RESUMEN
The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9-12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 µM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Estradiol/farmacología , Hormonas Esteroides Gonadales/deficiencia , Corazón/efectos de los fármacos , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Vasos Coronarios/fisiología , Endotelio Vascular/fisiología , Femenino , Masculino , Orquiectomía , Ovariectomía , Ratas , Ratas WistarRESUMEN
Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.
Asunto(s)
Androstenos/administración & dosificación , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Estradiol/administración & dosificación , Terapia de Reemplazo de Hormonas/métodos , Hipertensión/tratamiento farmacológico , Vasodilatación/efectos de los fármacos , Animales , Western Blotting , Bradiquinina/farmacología , Terapia Combinada , Vasos Coronarios/patología , Receptor alfa de Estrógeno/efectos de los fármacos , Estrógenos/administración & dosificación , Etidio/análogos & derivados , Femenino , Arteria Femoral , Hemodinámica , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Ovariectomía , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas , Ratas Endogámicas SHR , Vasodilatadores/farmacologíaRESUMEN
Drospirenone (DRSP) is a progestin with anti-aldosterone properties and it reduces blood pressure in hypertensive women. However, the effects of DRSP on endothelium-dependent coronary vasodilation have not been evaluated. This study investigated the effects of combined therapy with estrogen (E2) and DRSP on endothelium-dependent vasodilation of the coronary bed of ovariectomized (OVX) spontaneously hypertensive rats. Female spontaneously hypertensive rats (n=87) at 12 weeks of age were randomly divided into sham operated (Sham), OVX, OVX treated with E2 (E2), and OVX treated with E2 and DRSP (E2+DRSP) groups. Hemodynamic parameters were directly evaluated by catheter insertion into the femoral artery. Endothelium-dependent vasodilation in response to bradykinin in the coronary arterial bed was assessed using isolated hearts according to a modified Langendorff method. Coronary protein expression of endothelial nitric oxide synthase and estrogen receptor alpha (ER-α) was assessed by Western blotting. Histological slices of coronary arteries were stained with hematoxylin and eosin, and morphometric parameters were analyzed. Oxidative stress was assessed in situ by dihydroethidium fluorescence. Ovariectomy increased systolic blood pressure, which was only prevented by E2+DRSP treatment. Estrogen deficiency caused endothelial dysfunction, which was prevented by both treatments. However, the vasodilator response in the E2+DRSP group was significantly higher at the three highest concentrations compared with the OVX group. Reduced ER-α expression in OVX rats was restored by both treatments. Morphometric parameters and oxidative stress were augmented by OVX and reduced by E2 and E2+DRSP treatments. Hormonal therapy with E2 and DRSP may be an important therapeutic option in the prevention of coronary heart disease in hypertensive post-menopausal women.
Asunto(s)
Animales , Femenino , Ratas , Androstenos/administración & dosificación , Vasos Coronarios/efectos de los fármacos , Endotelio Vascular/efectos de los fármacos , Estradiol/administración & dosificación , Terapia de Reemplazo de Hormonas/métodos , Hipertensión/tratamiento farmacológico , Vasodilatación/efectos de los fármacos , Western Blotting , Bradiquinina/farmacología , Terapia Combinada , Vasos Coronarios/patología , Receptor alfa de Estrógeno/efectos de los fármacos , Estrógenos/administración & dosificación , Etidio/análogos & derivados , Arteria Femoral , Hemodinámica , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Óxido Nítrico Sintasa de Tipo III/efectos de los fármacos , Ovariectomía , Estrés Oxidativo/efectos de los fármacos , Distribución Aleatoria , Ratas Endogámicas SHR , Vasodilatadores/farmacologíaRESUMEN
The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9−12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.
Asunto(s)
Animales , Masculino , Femenino , Ratas , Hormonas Esteroides Gonadales/deficiencia , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Endotelio Vascular/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Estradiol/farmacología , Corazón/efectos de los fármacos , Endotelio Vascular/fisiología , Orquiectomía , Ovariectomía , Ratas Wistar , Vasos Coronarios/fisiologíaRESUMEN
BACKGROUND: There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs). METHODOLOGY/PRINCIPAL FINDINGS: Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats. CONCLUSION: Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.
Asunto(s)
Cardiomegalia/enzimología , Cardiomegalia/fisiopatología , Hormonas Esteroides Gonadales/farmacología , Hipertensión/enzimología , Contracción Miocárdica/efectos de los fármacos , Peptidil-Dipeptidasa A/metabolismo , Enzima Convertidora de Angiotensina 2 , Animales , Presión Sanguínea/efectos de los fármacos , Western Blotting , Peso Corporal/efectos de los fármacos , Cardiomegalia/complicaciones , Densitometría , Femenino , Gónadas/efectos de los fármacos , Gónadas/cirugía , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hemodinámica/efectos de los fármacos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas Endogámicas SHR , Sístole/efectos de los fármacosRESUMEN
The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17ß-estradiol benzoate (OVE, 2.0 mg · kg(-1) · day(-1), sc) and progesterone (OVP, 1.7 mg · kg(-1) · day(-1), sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17ß-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6 ± 36.1 ng/g) and denervated rat groups (D: 102.1 ± 15.7; ODE: 108.7 ± 23.2; ODP: 101.1 ± 22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9 ± 25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.
Asunto(s)
Catecolaminas/metabolismo , Cloro/metabolismo , Estrógenos/fisiología , Riñón/inervación , Progesterona/fisiología , Sodio/metabolismo , Animales , Peso Corporal/fisiología , Catecolaminas/sangre , Desnervación , Femenino , Tasa de Filtración Glomerular/fisiología , Riñón/metabolismo , Ovariectomía , Ratas Wistar , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
The maintenance of extracellular Na+ and Cl- concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na+ and Cl- reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg-1·day-1, sc) and progesterone (OVP, 1.7 mg·kg-1·day-1, sc). We assessed Na+ and Cl- fractional excretion (FENa+ and FECl- , respectively) and renal and plasma catecholamine release concentrations. FENa+ , FECl- , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FENa+ , FECl- , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function.
Asunto(s)
Animales , Femenino , Catecolaminas , Cloro/metabolismo , Estrógenos/fisiología , Riñón/inervación , Progesterona/fisiología , Sodio/metabolismo , Peso Corporal/fisiología , Catecolaminas/sangre , Desnervación , Tasa de Filtración Glomerular/fisiología , Riñón/metabolismo , Ovariectomía , Ratas Wistar , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Hipertensión/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangre , Animales , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Femenino , Hipertensión/fisiopatología , Masculino , Ovariectomía , Ratas Endogámicas SHR , Factores SexualesRESUMEN
Sex hormones modulate the action of both cytokines and the renin-angiotensin system. However, the effects of angiotensin I-converting enzyme (ACE) on the proinflammatory and anti-inflammatory cytokine levels in male and female spontaneously hypertensive rats (SHR) are unclear. We determined the relationship between ACE activity, cytokine levels and sex differences in SHR. Female (F) and male (M) SHR were divided into 4 experimental groups each (n = 7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage), castrated + vehicle, and castrated + enalapril. Treatment began 21 days after castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE activity than female rats. Castration reduced serum ACE in males but did not affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV = 16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV = 12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels were higher in females than in males. Ovariectomy reduced all cytokine levels and orchiectomy reduced IL-6 but increased IL-10 concentrations in males. Castration eliminated the differences in all inflammatory cytokine levels (IL-6 and TNF-α) between males and females. Enalapril increased IL-10 in all groups and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril eliminated the sexual dimorphisms of cytokine levels in SV animals, which suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive effects.
Asunto(s)
Animales , Femenino , Masculino , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Enalapril/farmacología , Hipertensión/sangre , /sangre , /sangre , Factor de Necrosis Tumoral alfa/sangre , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Hipertensión/fisiopatología , Ovariectomía , Ratas Endogámicas SHR , Factores SexualesRESUMEN
Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR). Female SHR were divided into four groups (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10 mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67%, respectively) in the OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg) when compared to the OVX group (P < 0.01) and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg) than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.
Asunto(s)
Vasos Coronarios/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Enfermedad de la Arteria Coronaria/prevención & control , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Femenino , Hipertensión/fisiopatología , Ovariectomía , Perfusión , Distribución Aleatoria , Ratas , Ratas Endogámicas SHRRESUMEN
Tamoxifen has been associated with a reduction in the incidence of myocardial infarction. However, the effects of tamoxifen on coronary reactivity have not been fully elucidated. The objective of this study was to determine the effects of chronic treatment with tamoxifen on coronary vascular reactivity in spontaneously hypertensive rats (SHR). Female SHR were divided into four groups (N = 7 each): sham-operated (SHAM), sham-operated and treated with tamoxifen (10 mg/kg) by gavage for 90 days (TAMOX), ovariectomized (OVX), and ovariectomized and treated with tamoxifen (OVX+TAMOX). Mean arterial pressure (MAP), heart rate (HR), coronary perfusion pressure (CPP), and coronary vascular reactivity were measured. MAP and HR were reduced (9.42 and 11.67 percent, respectively) in the OVX+TAMOX group compared to the OVX group (P < 0.01). The coronary vascular reactivity of the OVX+TAMOX group presented smaller vasoconstrictor responses to acetylcholine (2-64 µg) when compared to the OVX group (P < 0.01) and this response was similar to that of the SHAM group. The adenosine-induced vasodilator response was greater in the TAMOX group compared to the SHAM and OVX groups (P < 0.05). Baseline CPP was higher in OVX+TAMOX and TAMOX groups (136 ± 3.6 and 130 ± 1.5 mmHg) than in OVX and SHAM groups (96 ± 2 and 119 ± 2.3 mmHg; P < 0.01). Tamoxifen, when combined with OVX, attenuated the vasoconstriction induced by acetylcholine and increased the adenosine-induced vasodilatory response, as well as reducing the MAP, suggesting beneficial effects of tamoxifen therapy on coronary vascular reactivity after menopause.
Asunto(s)
Animales , Femenino , Ratas , Vasos Coronarios/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Tamoxifeno/farmacología , Presión Sanguínea/efectos de los fármacos , Enfermedad de la Arteria Coronaria/prevención & control , Circulación Coronaria/efectos de los fármacos , Vasos Coronarios/fisiopatología , Modelos Animales de Enfermedad , Hipertensión/fisiopatología , Ovariectomía , Perfusión , Distribución Aleatoria , Ratas Endogámicas SHRRESUMEN
AIM: The relaxation induced by oestrogen in the coronary vascular bed from normotensive rats has been well described. However, almost nothing is known about this action in spontaneously hypertensive rats (SHR). We investigated the effect of 17 ß-oestradiol (E(2) ) in coronary arteries from SHR as well as the contribution of the endothelium and the vascular smooth muscle to this action. METHODS: Coronary arteries from male and female rats were used. Mean arterial pressure (MAP) and baseline coronary perfusion pressure (CPP) were determined. The effects of 10 µm E(2) were assessed by in bolus administration before and after endothelium denudation (0.25 µm sodium deoxycholate) or perfusion with 100 µm N(ω)-nitro-L-arginine methyl ester (L-NAME), 2.8 µm indomethacin, 0.75 µm clotrimazole, 100 µm L-NAME after endothelium denudation (0.25 µm sodium deoxycholate), 100 µm L-NAME plus 2.8 µm indomethacin, 0.75 µm clotrimazole plus 2.8 µm indomethacin and 4 mm tetraethylammonium (TEA). RESULTS: MAP was higher in the male group, while CPP was higher in the female group (P<0.05). There were no differences in E(2)-induced relaxation between females and males (-17±1.6 vs. -17±2% respectively). Only in the female group the E(2) response was significantly attenuated after endothelium removal or perfusion with clotrimazole. The response to E(2) was reduced in both groups with L-NAME, L-NAME plus indomethacin, L-NAME after endothelium removal or TEA. CONCLUSIONS: Nitric oxide, endothelium-derived hyperpolarizing factor and potassium channels may have the most important role to E(2) response in the female group, whereas nitric oxide and potassium channels may have the most important role in the male group.
Asunto(s)
Vasos Coronarios/metabolismo , Endotelio Vascular/metabolismo , Estradiol/metabolismo , Hipertensión/metabolismo , Músculo Liso Vascular/metabolismo , Vasodilatación , Animales , Factores Biológicos/metabolismo , Presión Sanguínea , Vasos Coronarios/efectos de los fármacos , Vasos Coronarios/fisiopatología , Inhibidores de la Ciclooxigenasa/farmacología , Modelos Animales de Enfermedad , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiopatología , Inhibidores Enzimáticos/farmacología , Femenino , Hipertensión/fisiopatología , Masculino , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiopatología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Perfusión , Bloqueadores de los Canales de Potasio/farmacología , Canales de Potasio/metabolismo , Ratas , Ratas Endogámicas SHR , Factores Sexuales , Vasodilatación/efectos de los fármacosRESUMEN
Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 +/- 4 vs D: 115 +/- 4 mmHg) or HR (S: 340 +/- 12 vs D: 368 +/- 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 +/- 1 mmHg and -16 +/- 2 bpm vs D: -16 +/- 1 mmHg and 9 +/- 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 +/- 9%) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.
Asunto(s)
Presión Sanguínea/fisiología , Diuresis/fisiología , Frecuencia Cardíaca/fisiología , Riñón/inervación , Apnea Obstructiva del Sueño/fisiopatología , Simpatectomía , Enfermedad Aguda , Animales , Hipotensión/fisiopatología , Riñón/fisiopatología , Masculino , Natriuresis/fisiología , Ratas , Ratas Wistar , Índice de Severidad de la Enfermedad , OrinaRESUMEN
OBJETIVOS: Investigar as implicações da lipoclasia dermossônica (LCD), lipólise do tecido adiposo branco subcutâneo induzido por ultrassom (US), no metabolismo energético e na composição corporal de ratos saudáveis. MÉTODOS: Utilizaram-se 20 ratos Wistar saudáveis, com 4 meses de idade, pesando ±380g, divididos aleatoriamente em 2 grupos: 1) controle-sham (CS), 2) terapia ultrassônica de baixa intensidade (TUSBI). Durante 10 dias, após sedação (halotano-3 por cento vaporizado), os animais eram submetidos à TUSBI (I SATA=3MHz, 1W.cm-2, modo pulsado 2:8ms, ciclo de 30 por cento por 3 minutos) em região infra-abdominal e inguinal. Medidas de peso, comprimento naso-anal e parâmetros metabólicos (ingestão e excreção) foram controlados durante o estudo. Ao final do tratamento, amostras de sangue foram coletadas para dosagens bioquímicas, e então avaliadas adiposidades retroperitoneal (RET), perirenal (PR), epididimal (EP) e inguinal (ING). O HOMA-IR (homeostasis model assessment) foi calculado para estimar resistência insulínica (RI). Para análise estatística, utilizou-se ANOVA, teste de Tukey e teste t de Student, com diferenças estabelecidas em p<0,05. RESULTADOS: No peso corporal, não houve alteração nos animais CS (384±9g), no entanto reduziu (p<0,01) no grupo TUSBI (337±2g), assim como a ingestão de comida (25±1g) vs.(21±1g). Houve ainda reduções (p<0,05) nos coxins RET, PR e ING, índice de obesidade, níveis de triglicerídeos e lipoproteínas plasmáticas. A hiperinsulinemia, sem alterações da glicemia, caracterizou estado de RI confirmado pelo HOMA-IR. CONCLUSÕES: A LDC reduziu a ingestão de comida e o peso corporal, além de modificar a deposição de gordura nos depósitos RET, PR e ING em ratos, o que alterou o perfil lipoprotéico produzindo importante quadro de RI.
OBJECTIVES: To investigate the implications of Dermosonic lipoclasis (DLC), i.e. lipolysis on subcutaneous white adipose tissue induced by ultrasound, for the energy metabolism and body composition of healthy rats. METHODS: Twenty four-month-old male Wistar rats weighting ±380g were randomly divided into two groups: 1) sham control (SC) and 2) low-intensity ultrasound therapy (LIUST). For 10 days, after sedation with 3 percent vaporized halothane, the animals underwent LIUST (I SATA =3MHz, 1 Wcm-2, pulsed mode 2:8ms, 30 percent cycles for 3 minutes) in the infra-abdominal and inguinal regions. Weight measurements, naso-anal length and metabolic parameters (food and water intake and excretion) were monitored during the study. At the end of the treatment, blood samples were collected for biochemical analyses. Retroperitoneal (RET), perirenal (PR), epididymal (EP) and inguinal (ING) adiposity was evaluated. HOMA-IR (homeostasis model assessment) was calculated to estimate insulin resistance. For statistical analyses, the Student t test, ANOVA and the Tukey test were used, and differences were established as p<0.05. RESULTS: Regarding body weight, the SC group (384±9g) did not show any changes, while the treated group (337±2g) showed reductions (p<0.01). This was also seen in relation to food intake: (25±1g) vs. (21±1g). There were also reductions (p<0.05) in the RET, PR and ING fat-pads, obesity index, triglyceride levels and plasma lipoprotein levels. Hyperinsulinemia without changes in glycemia characterized a state of insulin resistance, which was confirmed by HOMA-IR. CONCLUSIONS: DLC reduced the food intake and body weight and modified the fat deposition in the RET, PR and ING stores in rats. This changed the lipid profile to produce a significant state of insulin resistance.
RESUMEN
Obstructive apnea (OA) can exert significant effects on renal sympathetic nerve activity (RSNA) and hemodynamic parameters. The present study focuses on the modulatory actions of RSNA on OA-induced sodium and water retention. The experiments were performed in renal-denervated rats (D; N = 9), which were compared to sham (S; N = 9) rats. Mean arterial pressure (MAP) and heart rate (HR) were assessed via an intrafemoral catheter. A catheter was inserted into the bladder for urinary measurements. OA episodes were induced via occlusion of the catheter inserted into the trachea. After an equilibration period, OA was induced for 20 s every 2 min and the changes in urine, MAP, HR and RSNA were recorded. Renal denervation did not alter resting MAP (S: 113 ± 4 vs D: 115 ± 4 mmHg) or HR (S: 340 ± 12 vs D: 368 ± 11 bpm). An OA episode resulted in decreased HR and MAP in both groups, but D rats showed exacerbated hypotension and attenuated bradycardia (S: -12 ± 1 mmHg and -16 ± 2 bpm vs D: -16 ± 1 mmHg and 9 ± 2 bpm; P < 0.01). The basal urinary parameters did not change during or after OA in S rats. However, D rats showed significant increases both during and after OA. Renal sympathetic nerve activity in S rats increased (34 ± 9 percent) during apnea episodes. These results indicate that renal denervation induces elevations of sodium content and urine volume and alters bradycardia and hypotension patterns during total OA in unconscious rats.
Asunto(s)
Animales , Masculino , Ratas , Presión Sanguínea/fisiología , Diuresis/fisiología , Frecuencia Cardíaca/fisiología , Riñón/inervación , Simpatectomía , Apnea Obstructiva del Sueño/fisiopatología , Enfermedad Aguda , Hipotensión/fisiopatología , Riñón/fisiopatología , Natriuresis/fisiología , Ratas Wistar , Índice de Severidad de la Enfermedad , OrinaRESUMEN
1. The aim of the present study was to evaluate the effect of treatment with enalapril on the sensitivity of cardiopulmonary reflexes 30 days after myocardial infarction in Wistar rats. 2. Animals were divided into four groups: (i) sham operated, receiving vehicle (SHAM); (ii) infarcted, receiving vehicle (0.9% NaCl; INF); (iii) sham operated, receiving enalapril (SHAME); and (iv) infarcted, receiving enalapril (INFE). 3. Enalapril was administered at a dose of 10 mg/kg per day. Serotonin (4-32 microg/kg, i.v.) was administered in order to activate the Bezold-Jarisch reflex, which was estimated as the percentage of reduction in heart rate. 4. The volume-sensitive cardiopulmonary reflex was induced by saline overload and evaluated as the percentage increase in sodium and volume renal excretion. At the end of the experiments, rats were killed and hearts excised to estimate the size of the infarction. The weight of the kidneys, lungs, liver and cardiac chambers as ratios of bodyweight was used to estimate the extent of hypertrophy. 5. The results showed an impairment in the sensitivity of the cardiopulmonary reflexes in the INF group compared with the SHAM and SHAME groups. We observed right ventricle and pulmonary hypertrophy, a reduction in mean and systolic arterial pressure and an increase in heart rate in INF animals. In the INFE group, nearly all the parameters were normal compared with the INF group, except for systolic arterial pressure, which was only partially improved. 6. The main finding of the present study was that treatment with enalapril normalized the sensitivity of the cardiopulmonary reflexes, which could be due, in part, to the reduction of cardiac hypertrophy. The present study provides information about the beneficial effects of the angiotensin-converting enzyme inhibitors by normalizing the cardiopulmonary reflexes involved with the regulation of volume and sodium, as well as control of arterial pressure and heart rate in infarcted animals.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Cardiomegalia/prevención & control , Enalapril/farmacología , Riñón/inervación , Pulmón/inervación , Infarto del Miocardio/tratamiento farmacológico , Reflejo/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Barorreflejo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Cardiomegalia/etiología , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Enfermedad Crónica , Modelos Animales de Enfermedad , Enalapril/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Natriuresis/efectos de los fármacos , Ratas , Ratas Wistar , Sistema Nervioso Simpático/fisiopatología , Micción/efectos de los fármacos , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm(2))-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 +/- 20 vs 63 +/- 8 mm(2)). The basal cellularity values on day 1 were: C = 763 +/- 47, L = 1116 +/- 85, D = 376 +/- 24, D + L = 698 +/- 31, X = 453 +/- 29, X + L = 639 +/- 32 U/mm(2). These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Terapia por Luz de Baja Intensidad , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Cicatrización de Heridas/efectos de la radiación , Animales , Celecoxib , Helio/uso terapéutico , Masculino , Ratones , Neón/uso terapéutico , Cicatrización de Heridas/efectos de los fármacosRESUMEN
We determined the effects of helium-neon (He-Ne) laser irradiation on wound healing dynamics in mice treated with steroidal and non-steroidal anti-inflammatory agents. Male albino mice, 28-32 g, were randomized into 6 groups of 6 animals each: control (C), He-Ne laser (L), dexamethasone (D), D + L, celecoxib (X), and X + L. D and X were injected im at doses of 5 and 22 mg/kg, respectively, 24 h before the experiment. A 1-cm long surgical wound was made with a scalpel on the abdomens of the mice. Animals from groups L, D + L and X + L were exposed to 4 J (cm²)-1 day-1 of He-Ne laser for 12 s and were sacrificed on days 1, 2, or 3 after the procedure, when skin samples were taken for histological examination. A significant increase of collagen synthesis was observed in group L compared with C (168 ± 20 vs 63 ± 8 mm²). The basal cellularity values on day 1 were: C = 763 ± 47, L = 1116 ± 85, D = 376 ± 24, D + L = 698 ± 31, X = 453 ± 29, X + L = 639 ± 32 U/mm². These data show that application of L increases while D and X decrease the inflammatory cellularity compared with C. They also show that L restores the diminished cellularity induced by the anti-inflammatory drugs. We suggest that He-Ne laser promotes collagen formation and restores the baseline cellularity after pharmacological inhibition, indicating new perspectives for laser therapy aiming to increase the healing process when anti-inflammatory drugs are used.
Asunto(s)
Animales , Masculino , Ratones , Antiinflamatorios/uso terapéutico , Dexametasona/uso terapéutico , Terapia por Luz de Baja Intensidad , Pirazoles/uso terapéutico , Sulfonamidas/uso terapéutico , Cicatrización de Heridas/efectos de la radiación , Helio/uso terapéutico , Neón/uso terapéutico , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Epidemiological and clinical evidence suggests that a judicious diet, regular physical activity and blood pressure (BP) monitoring must start in early childhood to minimize the impact of modifiable cardiovascular risk factors. This study was designed to evaluate BP and metabolic parameters of schoolchildren from Vitória, Espírito Santo State, Brazil, and correlate them with cardiovascular risk factors. The study was conducted on 380 students aged 10-14 years (177 boys, 203 girls) enrolled in public schools. Baseline measurements included body mass index, BP and heart rate. The students were submitted to exercise spirometry on a treadmill. VO2max was obtained from exercise testing to voluntary exhaustion. Fasting serum total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), and glucose were measured. Nine point nine percent of the boys and 11.7% of the girls were hypertensive or had pre-hypertensive levels. There was no significant correlation between VO2max and TC, LDL-C, or TG in prepubertal children, but a slight negative correlation was detected in post-pubertal boys for HDL-C and TG. In addition, children with hypertension (3.4%) or pre-hypertensive levels (6.6%) also had comorbidity for overweight and blood lipid abnormalities (14% for triglycerides, 44.7% for TC, 25.9% for LDL-C, 52% for low HDL-C). The present study shows for the first time high correlations between prehypertensive blood pressure levels and the cardiovascular risk factors high TC, high LDL-C, low HDL-C in schoolchildren. These are important for the formulation of public health policies and strategies.