RESUMO
BACKGROUND: Post-operative nausea and vomiting (PONV) is a common complication of anaesthesia. This study was conducted in 100 German and 100 Turkish patients scheduled for elective surgery under general anaesthesia to assess the amount patients were willing to pay for an anti-emetic that completely prevented PONV. METHODS: Post-operatively, using Dixon's up and down method, patients completed an interactive computer questionnaire with a random starting point to determine how much of their own money they were willing to pay for a totally effective anti-emetic treatment. RESULTS: On average, participants were willing to pay 65 euro in Germany and 68 euro in Turkey to avoid PONV. However, patients who actually experienced PONV were willing to pay larger amounts: 96 euro in Germany and 99 euro in Turkey. The amount patients were willing to pay was related to female sex, history of motion sickness, non-smoking status and better education. CONCLUSIONS: Despite differences in political and cultural origin, health care system and financial background, the amount patients were willing to pay for an effective anti-emetic was similar in both Germany and Turkey to that reported previously for the USA.
Assuntos
Antieméticos/economia , Financiamento Pessoal , Náusea e Vômito Pós-Operatórios/prevenção & controle , Adulto , Anestesia Geral , Antieméticos/uso terapêutico , Custos de Medicamentos , Feminino , Alemanha , Humanos , Masculino , Náusea e Vômito Pós-Operatórios/economia , Náusea e Vômito Pós-Operatórios/psicologia , Inquéritos e Questionários , TurquiaRESUMO
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) share a common receptor. LH/hCG receptors, located in the vascular smooth muscle and endothelial cells of uterine blood vessels, are most numerous in smaller intramyometrial vessels and are cyclic in nature. There is a correlation between hCG levels and decreased uterine vascular resistance in humans, and in pseudopregnant rats, hCG decreases uterine blood flow. We found that systemic administration of hCG to cycling rats reduced uterine blood flow within 20 minutes on all days of the estrous cycle when flow was measured via the radioactive microsphere method. This effect was absent in ovariectomized rats. To determine the response to hCG at the microvascular level, we measured uterine arteriolar diameters in vivo via videomicroscopy after direct application or injection of hCG in rats on diestrus-1, diestrus-2, and proestrus. When hCG was suffused over the uterus (20 IU/60 mL), the uterine arterioles in diestrus (1 and 2) rats dilated but in proestrus rats were constricted. Neither response was altered in animals whose ovaries were removed 3 hours previously. An intraperitoneal injection of hCG (50 IU) caused uterine arteriolar constriction in diestrus-2 and proestrus animals but no change in diestrus-1. In ovariectomized rats, uterine arteriolar constriction following hCG injection was absent. Thus, the response of the uterine vasculature is not only cycle day dependent but also dependent on the route of administration. The effect of hCG on uterine blood flow in the rat may be a direct action of hCG, or it could be secondary to the release of other vasoactive substances known to be released by hCG. hCG might also alter blood flow by inducing angiogenesis.
Assuntos
Gonadotropina Coriônica/farmacologia , Hormônio Luteinizante/farmacologia , Modelos Animais , Útero/irrigação sanguínea , Animais , Feminino , Humanos , Microcirculação/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Ovariectomia , Ratos , Receptores do LH/análise , Receptores do LH/química , Receptores do LH/fisiologiaRESUMO
Isolated uterine vascular beds from virgin and pregnant rats were used to assess vascular reactivity and the ability of nitric oxide (NO), prostanoids and endothelium-derived hyperpolarizing factor (EDHF) to modulate these responses. One uterine horn from female rats in each oestrous cycle day and gestation day 17 was removed and perfused with physiological saline solution. Tone was induced with cirazoline (1 micromol/l), and concentration-response curves to acetylcholine (ACh) generated. Responsiveness to ACh was tested in the presence of N-nitro-L-arginine (L-NA), ibuprofen (IBU) and tetrabutylammonium (TBA), to inhibit NO synthase, cyclo-oxygenase and K+ channels respectively. Cirazoline-induced tone was smaller in the pregnant compared with the proestrous group. Sensitivity to ACh was cycle day and pregnancy dependent with pregnant > dioestrous day-1 > dioestrous day-2 > proestrous and oestrous. L-NA shifted the curve to the right in all groups except dioestrous day-1. IBU inhibited the ACh response in the pregnant group only. TBA virtually abolished the response in all groups. These results suggest that in the uterine vascular bed from pregnant rats, EDHF, along with NO and a dilator prostanoid mediate ACh-induced dilatation. In contrast, in the dioestrous day-1 group, only EDHF seems to be released by ACh in this vascular bed. In the oestrous, dioestrous day-2 and proestrous groups, ACh releases both EDHF and NO.
Assuntos
Estro , Útero/irrigação sanguínea , Acetilcolina/farmacologia , Agonistas Adrenérgicos/farmacologia , Animais , Fatores Biológicos/fisiologia , Inibidores de Ciclo-Oxigenase/farmacologia , Diestro , Inibidores Enzimáticos/farmacologia , Feminino , Idade Gestacional , Ibuprofeno/farmacologia , Imidazóis/farmacologia , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Bloqueadores dos Canais de Potássio , Gravidez , Proestro , Prostaglandinas/fisiologia , Compostos de Amônio Quaternário/farmacologia , Ratos , Ratos Sprague-Dawley , Útero/efeitos dos fármacosRESUMO
OBJECTIVE: The aim of this study was to compare reactivity of uterine arterioles in vivo between virgin and gravid rats. STUDY DESIGN: In anesthetized gravid and virgin rats circumferential arterioles were observed by videomicroscopy while vasoactive agonists were suffused over the uterus. Arteriolar diameter changes were compared. RESULTS: Resting and maximum diameters of circumferential arterioles were significantly larger in pregnant animals. Sensitivity to acetylcholine was greater in pregnant animals than in virgin animals (50% effective concentration, 7.1 +/- 0.17 negative log mol/L vs 6.1 +/- 0.32 negative log mol/L), whereas that to phenylephrine was less (50% effective concentration, 5.3 +/- 0.11 negative log mol/L vs 6.0 +/- 0.17 negative log mol/L). Angiotensin II-induced constriction was significantly reduced in pregnant rats only at lower concentrations. Serotonin significantly dilated arterioles in virgin rats (76% +/- 3% of maximum) but caused significant arteriolar constriction in pregnant animals (65% +/- 4% of maximum). CONCLUSION: The in vivo uterine microcirculatory preparation allows measurement of resistance vessels in the intact animal. Although these results differ from some previous reports, differences may be attributable to vessel location or to in vivo versus in vitro conditions.
Assuntos
Arteríolas/fisiologia , Prenhez/fisiologia , Útero/irrigação sanguínea , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Acetilcolina/administração & dosagem , Acetilcolina/farmacologia , Angiotensina II/administração & dosagem , Angiotensina II/farmacologia , Animais , Arteríolas/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Microscopia de Vídeo , Fenilefrina/administração & dosagem , Fenilefrina/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley , Serotonina/administração & dosagem , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
In isolated, perfused mesenteric vascular beds from female rats, it was assessed whether the constrictor response to cirazoline, an alpha(1)-adrenergic agonist, or acetylcholine (ACh)-induced relaxation was altered by oestrous cycle or pregnancy and the ability of nitric oxide (NO), prostanoids and endothelium-derived hyperpolarizing factor (EDHF) to modulate these responses. Mesenteries, removed from female rats on each oestrous cycle day and gestation day 16, were perfused with physiological salt solution. Tone was induced with cirazoline (1 micromol/l), and concentration-response curves to ACh generated. Responsiveness to ACh was tested in the presence of N(omega)-nitro-L-arginine (L-NA), ibuprofen (IBU) and tetrabutylammonium (TBA), to inhibit nitric oxide synthase (NOS), cyclo-oxygenase and K(+) channels respectively. Cirazoline-induced tone was smaller in pro-oestrous and pregnant groups, but the increase in tone to L-NA was larger in pregnant compared with oestrous and dioestrous groups. Control responses to ACh were not different, but L-NA attenuated the response in virgin groups only. IBU did not affect the ACh response, but TBA attenuated it in all groups. When TBA was introduced first, ACh-induced dilatation was significantly reduced and not altered by L-NA addition. These results suggest that in the mesenteric vascular bed from cycling and pregnant rats, EDHF is the major mediator of ACh-induced dilatation and NOS may be up-regulated in pregnant and pro-oestrous rats.
Assuntos
Estro/fisiologia , Prenhez/fisiologia , Circulação Esplâncnica/fisiologia , Acetilcolina/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Animais , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Ibuprofeno/farmacologia , Imidazóis/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Bloqueadores dos Canais de Potássio , Gravidez , Compostos de Amônio Quaternário/farmacologia , Ratos , Ratos Sprague-Dawley , Vasoconstrição/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
The importance of nitric oxide (NO) and dilator prostaglandins in uterine resistance arterioles was investigated. In pentobarbital anaesthetized rats at dioestrus-2, the uterine microcirculation in vivo was transilluminated by a fibreoptic probe and microvessels (circumferential arterioles) viewed by video microscopy. Arteriolar diameters were measured while increasing concentrations of acetylcholine (ACh), serotonin (5-HT), phenylephrine (PE), or angiotensin II (AII) were applied topically (suffused) over the uterus. Agonists were applied alone or with ibuprofen (IBU; cyclooxygenase inhibitor), N omega-nitro-L-arginine (L-NA; nitric oxide synthase inhibitor) or both. Circumferential arterioles were dilated by ACh and 5-HT (10(-8)-10(-4) mol l-1) and constricted by PE (10(-8)-10(-5) mol l-1) and AII (10(-11)-10(-7) mol l-1). Suffusion of L-NA or L-NA with ibuprofen (10(-4) mol l-1 each) abolished ACh-induced dilation; ibuprofen alone blocked dilation at higher ACh concentrations. Serotonin-induced relaxation was significantly attenuated by L-NA alone or in combination with ibuprofen. Vasoconstriction induced by PE was enhanced by L-NA alone and L-NA with ibuprofen, but ibuprofen alone had no effect. In contrast, AII-induced constriction was enhanced significantly by ibuprofen or L-NA and further enhanced when both ibuprofen and L-NA were present. These results suggest that ACh can release either nitric oxide (NO) or cyclooxygenase products to cause uterine arteriolar dilation and that 5-HT-induced uterine microvascular relaxation is mediated via NO only. They also suggest that PE-induced vasoconstriction is attenuated by the release of NO but not cyclooxygenase products and that constrictor responses evoked by AII are attenuated by both NO and dilator prostaglandin release. Thus, both nitric oxide and dilator prostaglandins are important in the control of uterine microvessels.
Assuntos
Microcirculação/fisiologia , Óxido Nítrico/fisiologia , Prostaglandina-Endoperóxido Sintases/fisiologia , Útero/irrigação sanguínea , Acetilcolina/farmacologia , Angiotensina II/farmacologia , Animais , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Tecnologia de Fibra Óptica , Hemodinâmica/efeitos dos fármacos , Ibuprofeno/farmacologia , Microcirculação/efeitos dos fármacos , Microscopia de Vídeo , Óxido Nítrico Sintase/antagonistas & inibidores , Nitroarginina/farmacologia , Fenilefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: Our purpose was to investigate whether uterine microvascular responses to human chorionic gonadotropin application depend on route of administration and estrous cycle day. STUDY DESIGN: One uterine horn was exteriorized in pentobarbital-anesthetized cycling and ovariectomized rats and superfused with Krebs solution Uterine arterioles (64 +/- 2.1 microns) were viewed by videomicroscopy. Diameters were measured during a 20-minute baseline period and for 60 minutes during human chorionic gonadotropin suffusion (20 IU/60 ml) or 60 minutes after intraperitoneal injection of 50 IU of human chorionic gonadotropin. Papaverine (100 mumol/L) suffusion maximally dilated the uterine arterioles (80 +/- 2.6 microns). RESULTS: Suffusion of human chorionic gonadotropin-dilated arterioles on diestrus-1 (122% +/- 2% baseline) and diestrus-2 (118% +/- 4% baseline) but constricted arterioles on proestrus (78% +/- 7% baseline). Intraperitoneal injection of human chorionic gonadotropin resulted in arteriolar constriction on diestrus-2 (76% +/- 5% baseline) and proestrus (82% +/- 3% baseline). Ovariectomy eliminated the effects of injected but not suffused human chorionic gonadotropin. All results are significant at p < 0.05. CONCLUSIONS: Results indicate estrous cycle day-dependent direct and indirect effects of human chorionic gonadotropin on the resistance of uterine arterioles.
Assuntos
Gonadotropina Coriônica/administração & dosagem , Estro , Útero/irrigação sanguínea , Útero/efeitos dos fármacos , Animais , Arteríolas/anatomia & histologia , Arteríolas/efeitos dos fármacos , Feminino , Humanos , Masculino , Papaverina/farmacologia , Ratos , Ratos Sprague-Dawley , Vasodilatadores/farmacologiaRESUMO
We examined microvascular responses to acetylcholine (ACh), adenosine (ADO), nitroprusside (SNP), bradykinin (BK), histamine (HIS), and serotonin (5-HT) in control and diabetic rats. Agonists were applied topically to neurovascularly intact and environmentally controlled cremaster muscles of diabetic or control rats 3 weeks after streptozotocin or vehicle injection. Precapillary arteriolar diameters and leakage of fluorescein isothiocyanate conjugated to bovine serum albumin (FITC-BSA) in postcapillary venules were measured by using intravital microscopy techniques. All agents dilated the arterioles, and BK, HIS, and 5-HT caused concentration-dependent leakage of FITC-BSA. Of the vasodilators tested, only ACh-induced dilation was attenuated in diabetic animals. BK and HIS caused a concentration-dependent leakage of FITC-BSA that was similar in diabetic and control groups, but FITC-BSA leakage to 5-HT was significantly attenuated in diabetic animals. To determine whether the attenuated responses were attributable to an alteration of nitric oxide, the same dilational and leakage-promoting agents were tested in normoglycemic animals in the presence of N'-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. Only ACh-induced dilation in control animals was attenuated in the presence of L-NAME; all other responses were normal. Thus, although the attenuated ACh-induced arteriolar dilation in striated muscle of diabetic rats may be linked to an impairment of nitric oxide function or release, the reduced leakage to serotonin is not linked to nitric oxide. The impaired leakage response to 5-HT is specific for that agonist and is not an indication of a generalized decrease in vascular permeability in these diabetic animals.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Músculo Esquelético/irrigação sanguínea , Acetilcolina/farmacologia , Adenosina/farmacologia , Animais , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Bradicinina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Histamina/farmacologia , Masculino , Microcirculação/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Nitroprussiato/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
OBJECTIVE: Our purpose was to develop a method for direct measurement of rat uterine microvessels and to test their viability. STUDY DESIGN: In anesthetized female Sprague-Dawley diestrus rats, one uterine hom was isolated from the body cavity with its nerve and blood supply intact. A small fiberoptic probe inserted into the lumen of the uterus served as a light source for transillumination of uterine vessels. Diameters of circumferential arterioles were observed while increasing concentrations of vasoactive agonists were suffused over the uterus. RESULTS: No significant diameter changes occurred in circumferential arterioles of the control group (100-minute suffusion of Krebs solution). Dilation with papaverine (100 mumol/L) demonstrated that vessels possessed basal tone. Circumferential arterioles showed concentration-dependent constriction to phenylephrine and angiotensin II and dilation to acetylcholine and serotonin. CONCLUSIONS: This uterine microcirculatory preparation provides a stable, reproducible model of a unique microcirculatory bed that responds to vasoactive agents in a manner similar to other microcirculatory beds.
Assuntos
Útero/irrigação sanguínea , Acetilcolina/farmacologia , Angiotensina II/farmacologia , Animais , Feminino , Ginecologia/métodos , Microcirculação/efeitos dos fármacos , Obstetrícia/métodos , Fenilefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/farmacologia , Contração Uterina , Útero/efeitos dos fármacos , Vasoconstrição , VasodilataçãoRESUMO
Microphotohemolysis is a new technique that has been used to determine the presence of alterations in the erythrocyte membrane. The method involves light activation through a microscope of a fluorescent dye-erythrocyte-buffer solution in a hemocytometer. The interaction of the light and dye result in the generation of toxic oxygen products which attack the membrane allowing water to enter the cell. As hemolysis occurs the optical density of the microscopic field decreases and this is recorded for later quantitation with an image analysis system. Maximal effect, time to half maximal effect and the slope of the hemolysis curve are determined. The goal of this study was to determine if microphotohemolysis could be used to detect differences in erythrocytes from animals with altered physiological states such as hypercholesterolemia, diabetes, and copper deficiency. These are conditions that alter the lipid or protein structure of the erythrocyte membrane and/or the antioxidative capacity of the erythrocyte. There were no effects of hypercholesterolemia on the microphotohemolytic response of the erythrocyte. Streptozotocin-induced diabetes resulted in a decreased maximum effect, a significant shift of the hemolysis curve to the right (increased T 1/2) and a significant decrease in the slope of the hemolysis curve. Copper deficiency resulted in a significant decrease in the slope of the hemolysis curve. These results in diabetes and copper deficiency are consistent with an altered protein structure in the erythrocyte membrane that occurs in these conditions. The data demonstrate that this technique may be used to detect differences between normal and altered erythrocytes. As such, it could be useful in monitoring the course of a disease or its treatment.
Assuntos
Cobre/deficiência , Diabetes Mellitus Experimental/sangue , Hemólise/efeitos da radiação , Luz , Animais , Glicemia/metabolismo , Membrana Eritrocítica/fisiologia , Hipercolesterolemia/sangue , Ratos , Ratos Sprague-DawleyRESUMO
Naftidrofuryl is commonly used in treatment of peripheral vascular disease. Its vasodilator action has been partly explained by its inhibitory effect of 5-HT2 receptors on peripheral arteries in vitro. The purpose of this study was to test in vivo whether naftidrofuryl selectively inhibits 5-hydroxytryptamine (5-HT)-mediated constriction of large arterioles in the peripheral microcirculation. This constriction appears to be 5-HT2 receptor-mediated. Three separate protocols were used to test the effects of naftidrofuryl: chronic injection (15 mg/kg, i.p., twice daily for 5-6 days; n = 7), acute intravenous (i.v.) infusion (15 mg/kg over 30 min; n = 7), or topical application (5 x 10(-8) M, n = 6; 5 x 10(-7) M, n = 5; 5 x 10(-6) M, n = 5; 10(-5) M, n = 7). Male Sprague-Dawley rats (145-185 g body weight) were anesthetized with sodium pentobarbital (50 mg/kg) and the cremaster muscle was prepared for intravital video microscopy. Diameter response of arterioles (70-120 microns) to increasing concentrations of locally applied 5-HT (10(-8)-10(-4) M) was assessed. In rats receiving no drug treatment, 5-HT caused vasoconstriction of arterioles beginning at 10(-6) M and reaching approximately 40% constriction at 10(-4) M. These vasoactive responses were not altered by chronic daily doses or an acute infusion of naftidrofuryl. 5-HT responses obtained with and without naftidrofuryl applied directly into the cremaster-bath also had little effect on the arteriole response at each of the four concentrations tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Nafronil/farmacologia , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/fisiologia , Técnicas In Vitro , Ketanserina/farmacologia , Masculino , Microcirculação/efeitos dos fármacos , Músculos/irrigação sanguínea , Nafronil/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/efeitos dos fármacosRESUMO
Television microscopy was used to quantitate in vivo the responses of skeletal muscle small arterioles to acetylcholine. Five groups of rats were used: normotensive and one (1K1C)- and two (2K1C)- kidney one clip renovascular hypertensive Sprague-Dawley rats (SDR), as well as WKY normotensive and spontaneously hypertensive (SHR) rats. Third-order arterioles dilated to acetylcholine with an EC50 of 3 x 10(-7) M in SDR and 10(-6) M in WKY animals. In contrast, the concentration-response curve to acetylcholine was shifted to the right (less reactive) by 100 fold in the 1K1C- and by 1000 fold in the 2K1C-hypertensives. The dose-responsive curve to acetylcholine was shifted 10-fold to the right in the SHR's compared to the WKY's. Because acetylcholine acts through endothelium-dependent mechanisms and because maximal vasodilation could be induced by an endothelium-independent vasodilator, Na-nitroprusside, in all but the 2K1C-group, we conclude that different forms of hypertension interfere to a variable degree with endothelium-dependent vasodilator mechanisms in the skeletal muscle microcirculation.
Assuntos
Acetilcolina/farmacologia , Arteríolas/efeitos dos fármacos , Hipertensão Renovascular/fisiopatologia , Músculos/irrigação sanguínea , Animais , Relação Dose-Resposta a Droga , Hipertensão Renovascular/etiologia , Masculino , Nitroprussiato/farmacologia , Concentração Osmolar , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , VasodilataçãoRESUMO
Serotonin (5-HT) dilates precapillary arterioles in skeletal muscle. The purpose of this study was to determine if 5-HT releases endothelium-derived relaxing factor (EDRF) in this tissue. Diameters of third-order arterioles (A3) in the cremaster muscle of pentobarbital-anesthetized rats were measured via videomicroscopy. Concentration-response curves for acetylcholine, nitroprusside and 5-HT were obtained before and after the application of either hydroquinone (5 x 10(-4) M) or NG-nitro-L-arginine (10(-4) M). The involvement of prostaglandins was eliminated by ibuprofen (10(-4) M). In one group, 5-HT (20 micrograms/kg) and NG-nitro-L-arginine were given i.v. (30 mg/kg). The non-EDRF-dependent vasodilator papaverine (10(-5) M) was applied at the end of the protocol to determine the maximal resting diameter. When applied topically, both hydroquinone and NG-nitro-L-arginine significantly inhibited the dilation induced by acetylcholine, but neither agent affected the dilation to nitroprusside or 5-HT. NG-Nitro-L-arginine (i.v.) attenuated acetylcholine-induced dilation but not the dilation to intravenous 5-HT. These data suggest that 5-HT-induced dilation of small arterioles in skeletal muscle is EDRF-independent.
Assuntos
Arteríolas/efeitos dos fármacos , Músculos/irrigação sanguínea , Óxido Nítrico/metabolismo , Serotonina/farmacologia , Vasodilatação/efeitos dos fármacos , Acetilcolina/farmacologia , Animais , Arginina/administração & dosagem , Arginina/análogos & derivados , Arginina/farmacologia , Relação Dose-Resposta a Droga , Hidroquinonas/farmacologia , Injeções Intravenosas , Masculino , Nitroarginina , Nitroprussiato/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/administração & dosagemRESUMO
This study examined the microvascular response to serotonin (5-hydroxytryptamine; 5-HT) in short-term streptozotocin-induced diabetic rats. 5-HT was applied topically to the neurovascularly intact and environmentally controlled cremaster muscle of the two-week diabetic rat. Intravital microscopy was used to measure the diameters of large arterioles (First-order; A1) and small arterioles (Third-order; A3), and the FITC-albumin leakage in small venules (Third-order; V3). The diabetic animals were divided into two groups based on the dilator capacity of the A3 arterioles: the Diabetic-Tone group had a dilator capacity of 98 +/- 14.5% compared to 11 +/- 4.1% for the Diabetic No-Tone animals. 5-HT caused significantly greater constriction of A1 arterioles in Diabetic-Tone animals (-40 +/- 6%) than in either the Control (-19 +/- 6%) or Diabetic No-Tone (-18 +/- 5%) animals. 5-HT dilated the A3 arterioles to a similar degree in both the Diabetic-Tone and Control groups, but the Diabetic No-Tone group did not dilate to 5-HT because the A3 arterioles in these animals possessed no basal tone. Control animals showed a large 5-HT concentration-dependent increase in leakage of albumin in V3 venules, but this response was inhibited in the Diabetic-Tone animals. The 5-HT-induced leakiness in the Diabetic No-Tone group was intermediate between the other two groups. These results show that large arteriole constriction and small venule permeability responses to 5-HT are altered early in the development of diabetes, and are different in those animals with and without basal arteriolar tone. These data suggest that streptozotocin-induced diabetes alters microvascular function in striated muscle by at least two different cellular mechanisms.
Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Microcirculação/efeitos dos fármacos , Serotonina/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Permeabilidade Capilar/efeitos dos fármacos , Masculino , Músculos/irrigação sanguínea , Ratos , Ratos EndogâmicosRESUMO
The effects of serotonin (5-HT) on the microvasculature of cremaster muscles were compared in decerebrate, ketamine- and pentobarbital-anesthetized rats. 5-HT-induced constriction of large distributing arterioles was enhanced in the ketamine- and pentobarbital-anesthetized rats. Precapillary arterioles of pentobarbital-anesthetized animals were more sensitive to 5-HT-induced dilation than either decerebrate or ketamine-anesthetized animals. The response of vessels to two 5-HT receptor antagonists (methysergide and LY53857) were unchanged by the anesthetics. Our findings suggest that both ketamine and pentobarbital enhance the microvascular response to 5-HT, but that these changes are not due to an alteration of receptor sensitivity.
Assuntos
Anestésicos/administração & dosagem , Arteríolas/efeitos dos fármacos , Serotonina/farmacologia , Anestésicos/farmacologia , Animais , Estado de Descerebração , Ergolinas/farmacologia , Injeções Intravenosas , Ketamina/farmacologia , Masculino , Metisergida/farmacologia , Concentração Osmolar , Pentobarbital/farmacologia , Ratos , Ratos Sprague-Dawley , Antagonistas da Serotonina , Vasoconstrição , VasodilataçãoRESUMO
While renovascular (1K1C) hypertension significantly attenuates small arteriole dilation to sepsis in skeletal muscle of rats, maximal dilation of these small arterioles is not altered in response to an endothelium-independent vasodilator (nitroprusside). This suggests that 1K1C hypertension modifies a receptor-level mechanism to reduce small arteriole vasodilation during sepsis. To test this hypothesis, we used hydroquinone (HQ) to block an endothelium-derived relaxing factor (EDRF) in skeletal muscle arterioles of sodium pentobarbital (45 mg/kg BW)-anesthetized 1K1C-renovascular hypertensive male Sprague-Dawley rats which were then made septic. We found that responses of large and small arterioles to sepsis were blunted in hypertensive rats and that these responses were unchanged during the presence of HQ. This suggests 1) that blockade of some vasodilator mechanisms does not unmask an enhanced vasoconstrictor influence during sepsis in 1K1C hypertension and 2) that EDRF mechanisms are blunted by 1K1C hypertension. To further test this second idea, we examined the responses of small arterioles to acetylcholine (ACH) in normotensive and renovascular (1K1C) hypertensive rats before and after EDRF blockade. Skeletal muscle small arterioles were essentially not reactive to ACH in the hypertensives and HQ did not change this response. However, some vasodilation in hypertensives occurred under very high ACH concentrations even during the presence of HQ. These data suggest that sepsis-induced small arteriole dilation in skeletal muscle is blunted because endothelium-mediated responses are impaired in renovascular hypertension. Nevertheless, EDRF-independent mechanisms appear to be left intact during this form of hypertension.
Assuntos
Endotélio Vascular/fisiopatologia , Infecções por Escherichia coli/fisiopatologia , Hipertensão Renal/fisiopatologia , Músculos/irrigação sanguínea , Acetilcolina/farmacologia , Animais , Modelos Animais de Doenças , Hidroquinonas/farmacologia , Masculino , Microcirculação , Óxido Nítrico/antagonistas & inibidores , Ratos , Ratos EndogâmicosRESUMO
In anesthetized guinea pigs, we examined heart rate, arterial pressure, and GABA levels in four brain regions after systemic administration of 3-mercaptopropionic acid, an inhibitor of GABA synthesis. After i.p. injection of 195 mg/kg, significant reductions in GABA were first noted at 15 minutes in the cerebellum (-39%), 30 minutes in the hypothalamus (-27%), 60 minutes in the medulla pons (-34%) and 90 minutes in the cerebral cortex (-43%). Cardiovascular function was unaltered at 15 minutes but heart rate and arterial pressure were both significantly elevated at 30 minutes. By 60 minutes, however, heart rate had fallen below control. Injection of a lower dose (97.5 mg/kg i.p.) of 3-MP produced significant increases in heart rate and arterial pressure in 4 of 11 guinea pigs tested. When GABA levels in the same four brain regions were examined at 90 minutes and compared to corresponding levels from vehicle-treated guinea pigs, significant reductions were seen only in the hypothalamus and only in those animals displaying tachycardia and pressor responses. These findings are consistent with our previous results indicating that decreased GABA levels in the hypothalamus and in the medulla pons are responsible for the increases and decreases in heart rate, respectively, seen after systemic administration of 3-mercaptopropionic acid.
Assuntos
Ácido 3-Mercaptopropiônico/farmacologia , Encéfalo/efeitos dos fármacos , Sistema Cardiovascular/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Encéfalo/metabolismo , Fenômenos Fisiológicos Cardiovasculares , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Cobaias , Frequência Cardíaca/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Cinética , Masculino , Bulbo/efeitos dos fármacos , Bulbo/metabolismoRESUMO
Vascular endothelial cells influence microvessel diameters in vivo and in vitro and participate in host-defense mechanisms during sepsis. We examined whether small arteriole dilation in skeletal muscle during high cardiac output bacteremia (HOB) and low cardiac output live Escherichia coli sepsis (LOS) is mediated by an endothelium-derived relaxing factor (EDRF). Local chemical blockade of EDRF by hydroquinone (HQ) substantially blunted acetylcholine-induced dilation of small arterioles. HQ also prevented large arteriole (55-135 microns) constriction and small arteriole (6-22 microns) dilation in the cremaster muscle of rats during HOB. In LOS, small arteriole dilation was also prevented by HQ but only during the early period when blood pressure was unchanged from baseline. HQ did not alter large arteriole constriction during LOS. We conclude that small arteriole vasodilation in skeletal muscle is mediated at least in part by EDRF during bacteremia. Because EDRF cannot mediate large arteriole constriction and because HQ blunted large arteriole constriction during HOB, we now suspect that HQ also interferes at least in part with some large arteriole vasoconstrictor mechanism, possibly leukotrienes or an endothelium-derived constricting factor, which mediates large arteriole constriction during HOB. Our data also suggest that large arteriole constriction during LOS is partly mediated by factors that are unaffected by HQ. The endothelium appears to play an important role in the microcirculatory responses of skeletal muscle to live E. coli sepsis through more than one mechanism.
Assuntos
Acetilcolina/farmacologia , Arteríolas/fisiopatologia , Infecções por Escherichia coli/fisiopatologia , Hemodinâmica , Músculos/irrigação sanguínea , Óxido Nítrico/fisiologia , Choque Séptico/fisiopatologia , Vasodilatação , Animais , Antiarrítmicos/farmacologia , Arteríolas/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hidroquinonas/farmacologia , Técnicas In Vitro , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiopatologia , Ratos , Ratos Endogâmicos , Vasodilatação/efeitos dos fármacosRESUMO
Etomidate is characterized by minimal systemic cardiovascular effects, but its effect on the microvasculature has not been assessed. We compared the microvasculature of etomidate-anesthetized animals to that of animals anesthetized with pentobarbital, since its effects on the microvasculature are known. Male Sprague-Dawley rats were anesthetized with etomidate or pentobarbital. The cremaster muscle was prepared for microscopic viewing, leaving the neural and vascular supply intact. Small arterioles were near their maximal diameters in etomidate-anesthetized rats, whereas the pentobarbital group had a large dilator capacity (maximal diameter-basal diameter/basal diameter). The effect on resting arteriolar diameters of endothelium-derived relaxing factor (EDRF) and prostaglandin synthesis inhibitors was tested. Dilator capacity was not affected by the EDRF inhibitor nitro-L-arginine, but it was significantly increased by mefenamic acid and ibuprofen in etomidate-anesthetized animals. To test whether dilator and constrictor mechanisms were normal, serotonin concentration-response curves were obtained in pentobarbital and etomidate-anesthetized animals with and without mefenamate or ibuprofen present. The dilation of small arterioles to serotonin in the etomidate groups with mefenamate or ibuprofen was not significantly different from that of the pentobarbital groups. Serotonin produced a comparable constriction of large arterioles in both anesthetic groups. The topical application of etomidate to the cremaster muscle did not affect arteriolar diameters. Thus, etomidate appears to trigger the release of dilator prostaglandins in striated muscle through a central or indirect mechanism.
Assuntos
Anestesia Intravenosa , Etomidato , Músculos/irrigação sanguínea , Prostaglandinas/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Masculino , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Óxido Nítrico/fisiologia , Pentobarbital , Ratos , Ratos Endogâmicos , Serotonina/fisiologia , Vasodilatação/fisiologiaRESUMO
Serotonin constricts large arterioles and dilates small arterioles in striated muscle. Our study aimed to identify the receptors that mediate this differential response. Rats were anesthetized with pentobarbital sodium, and the cremaster muscle was prepared for videomicroscopy. Serotonin, applied topically, caused a constriction of large (A1) arterioles that was attenuated by cyproheptadine, methysergide, and LY 53857 but not by MDL 7222, phentolamine, propranolol, or diphenhydramine. The 5-hydroxytryptamine (5-HT)-induced constriction of A1 arterioles was mimicked by alpha-CH3-5-HT but not by 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) or 5-carboxamidotryptamine (5-CT). In addition, 5-HT caused a dilation of small (A3 or A4) arterioles that was blocked by cyproheptadine and methysergide but not by LY 53857, MDL 7222, phentolamine, or propranolol. Diphenhydramine caused a slight increase in the small arteriole mean effective concentration to serotonin but did not change the maximal response. The serotonin-induced dilation of small arterioles was mimicked by 5-CT but not by alpha-CH3-5-HT or 8-OH-DPAT. These data indicate that the 5-HT-induced constriction of large A1 arterioles is mediated via a 5-HT2 or 5-HT1C receptor, whereas 5-HT-induced dilation of smaller arterioles appears to be mediated by a 5-HT1-like receptor.