RESUMEN
BACKGROUND: Postmenopausia and hypercholesterolemia are related to endothelial dysfunction, a pathogenic event in atherosclerosis. Soy protein reduces plasma cholesterol, but there is scanty information about its effect on endothelial function. OBJECTIVE: To evaluate the effect of isolated soy protein compared to caseinate on plasma lipoproteins and endothelial function in postmenopausal hypercholesterolemic women. DESIGN: Randomized, double-blind, cross-over trial. SETTING: Outpatient clinic of the Catholic University of Chile. SUBJECTS: Eighteen healthy, postmenopausal women with hypercholesterolemia were recruited, included and completed the protocol. INTERVENTIONS: During the trial, all patients followed a low fat/low cholesterol diet and were randomly assigned to receive isolated soy protein or matching caseinate for 4 weeks, and then the alternative treatment until week 8. At pre-study and at the end of the first and second period, plasma lipoprotein levels and endothelial function (flow-mediated dilatation (FMD) of the brachial artery) were evaluated. RESULTS: Plasma total and low density lipoprotein (LDL)-cholesterol concentration were significantly lower with the low fat/low cholesterol diet compared to pre-study, either with caseinate or soy protein. No significant differences in plasma lipid concentration between caseinate or soy protein interventions were observed. FMD did not change with the caseinate. In contrast, when soy protein was administered, FMD was significantly higher compared to pre-study (9.4+/-1.8% vs 5.3+/-1.2%; P<0.05) and compared to caseinate intervention (9.4+/-1.8% vs 4.9+/-1.5%; P<0.033). CONCLUSIONS: These results suggest that in postmenopausal hypercholesterolemic women, soy protein improves endothelial function, regardless of changes in plasma lipoproteins.
Asunto(s)
Colesterol/sangre , Endotelio Vascular/efectos de los fármacos , Hipercolesterolemia/dietoterapia , Proteínas de Soja/administración & dosificación , Anciano , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/patología , Caseínas/administración & dosificación , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Cruzados , Método Doble Ciego , Endotelio Vascular/fisiología , Femenino , Humanos , Hipercolesterolemia/fisiopatología , Persona de Mediana Edad , Posmenopausia , Proteínas de Soja/uso terapéutico , Ultrasonografía , Vasodilatación/efectos de los fármacosRESUMEN
The activities of Na-K-ATPase and Na-K-2Cl cotransporter (NKCC1) were studied in the aorta, heart, and skeletal muscle of streptozotocin (STZ)-induced diabetic rats and control rats. In the aortic rings of STZ rats, the Na-K-ATPase-dependent (86)Rb/K uptake was reduced to 60.0 +/- 5.5% of the control value (P < 0.01). However, Na-K-ATPase activity in soleus skeletal muscle fibers of STZ rats and paired control rats was similar, showing that the reduction of Na-K-ATPase activity in aortas of STZ rats is tissue specific. To functionally distinguish the contributions of ouabain-resistant (alpha(1)) and ouabain-sensitive (alpha(2) and alpha(3)) isoforms to the Na-K-ATPase activity in aortic rings, we used either a high (10(-3) M) or a low (10(-5) M) ouabain concentration during (86)Rb/K uptake. We found that the reduction in total Na-K-ATPase activity resulted from a dramatic decrement in ouabain-sensitive mediated (86)Rb/K uptake (26.0 +/- 3.9% of control, P < 0.01). Western blot analysis of membrane fractions from aortas of STZ rats demonstrated a significant reduction in protein levels of alpha(1)- and alpha(2)-catalytic isoforms (alpha(1) = 71.3 +/- 9.8% of control values, P < 0.05; alpha(2) = 44.5 +/- 11.3% of control, P < 0.01). In contrast, aortic rings from the STZ rats demonstrated an increase in NKCC1 activity (172.5 +/- 9.5%, P < 0.01); however, in heart tissue no difference in NKCC1 activity was seen between control and diabetic animals. Transport studies of endothelium-denuded or intact aortic rings demonstrated that the endothelium stimulates both Na-K-ATPase and Na-K-2Cl dependent (86)Rb/K uptake. The endothelium-dependent stimulation of Na-K-ATPase and Na-K-2Cl was not hampered by diabetes. We conclude that abnormal vascular vessel tone and function, reported in STZ-induced diabetic rats, may be related to ion transport abnormalities caused by changes in Na-K-ATPase and Na-K-2Cl activities.
Asunto(s)
Aorta/enzimología , Proteínas Portadoras/metabolismo , Diabetes Mellitus Experimental/metabolismo , Angiopatías Diabéticas/metabolismo , Isoenzimas/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Western Blotting , Bumetanida/farmacología , Diuréticos/farmacología , Endotelio Vascular/enzimología , Inhibidores Enzimáticos/farmacología , Hipertensión/metabolismo , Técnicas In Vitro , Isoenzimas/análisis , Isoenzimas/antagonistas & inhibidores , Masculino , Tono Muscular/fisiología , Músculo Liso Vascular/fisiología , Ouabaína/farmacología , Potasio/farmacocinética , Ratas , Ratas Sprague-Dawley , Radioisótopos de Rubidio , Simportadores de Cloruro de Sodio-Potasio , ATPasa Intercambiadora de Sodio-Potasio/análisis , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidoresRESUMEN
Endothelium controls vascular smooth muscle tone by secreting relaxing and contracting factors. There is a constant release of endothelium derived relaxing factors, mainly nitric oxide, a potent vasodilator, inhibitor of platelet aggregation, monocyte adhesion and smooth muscle proliferation. In addition, the endothelium may increase the release of NO in response to humoral stimulation by vasoactive substances such as acetylcholine, bradykinin or substance P. Although the endothelium releases a number of products, no single blood test has yet proved useful to determine normal endothelial function or as early abnormalities. The most useful test of endothelial function relies on the measurement of endothelium-dependent dilatation in response to pharmacological or physiologic stimuli. The alteration of this response is known as endothelial dysfunction and has been observed in a variety of circumstances related to cardiovascular risk. This review summarizes the evidence that sustains this association and emphasizes the clinical utility of assessing endothelial function presenting two clinical cases of hypercholesterolemia in which a high-resolution vascular ultrasound in the brachial artery was used.
Asunto(s)
Enfermedades Cardiovasculares/fisiopatología , Endotelio Vascular/fisiopatología , Adulto , Arteria Braquial/fisiopatología , Enfermedades Cardiovasculares/etiología , Preescolar , Endotelio Vascular/fisiología , Femenino , Humanos , Masculino , Relajación Muscular/fisiología , Músculo Liso Vascular/fisiología , Factores de Riesgo , Vasodilatación/fisiologíaRESUMEN
Endothelial dysfunction is associated with atherogenesis and oxidative stress in humans. In rat and rabbit blood vessels, wine polyphenol antioxidants induce vascular relaxation in vitro through the NO-cGMP pathway. To assess the effect of a regular high-fat diet (HFD) and moderate red wine consumption on endothelial function (EF), a study was performed in healthy male volunteers. EF was measured as flow-mediated dilatation of the brachial artery, employing high-resolution ultrasound after an overnight fast. Other clinical and biochemical parameters related to EF were also measured. Six volunteers received a control diet, rich in fruits and vegetables (27% calories as fat) and five volunteers received an HFD (39.5% calories as fat). Measurements were done twice on each volunteer: after a period of 30 d with diet plus 240 mL of red wine/d, and after a period of 30 d with diet, without wine. In the absence of wine, there is a reduction of EF with HFD when compared to the control diet (P = 0.014). This loss of EF is not seen when both diets are supplemented with wine for 30 d (P = 0.001). Plasma levels of n-3 fatty acids (R2 = 0.232, P = 0.023) and lycopene (R2 = 0.223, P = 0.020) show a positive correlation with individual EF measurements, but they do not account for the significant differences observed among dietary groups or after wine supplementation. These results help elucidate the deleterious effect of a high-fat diet and the protective role of wine, n-3 fatty acids and dietary antioxidants in cardiovascular disease.
Asunto(s)
Grasas de la Dieta/efectos adversos , Endotelio Vascular/fisiología , Vino , Fosfatasa Alcalina/sangre , Arteria Braquial/efectos de los fármacos , Arteria Braquial/fisiología , Dieta , Endotelio Vascular/efectos de los fármacos , Ácidos Grasos/sangre , Ácidos Grasos Omega-3/sangre , Frutas , Homocisteína/sangre , Humanos , Masculino , Nitroglicerina/farmacología , Transaminasas/sangre , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Verduras , Vitamina B 12/sangre , gamma-Glutamiltransferasa/sangreRESUMEN
Sarcoplasmic reticulum membrane vesicles isolated from frog skeletal muscle display high conductance calcium channels when fused into phospholipid bilayers. The channels are selective for calcium and barium over Tris. The fractional open time was voltage-independent (-40 to +25 mV), but was steeply dependent on the free cis [Ca2+] (P0 = 0.02 at 10 microM cis Ca2+ and 0.77 at 150 microM Ca2+; estimated Hill coefficient: 1.6). Addition of ATP (1 mM; cis) further increased P0 from 0.77 to 0.94. Calcium activation was reversed by addition of EGTA to the cis compartment. Magnesium (2 mM) increased the frequency of rapid closures and 8 mM magnesium decreased the current amplitude from 3.4 to 1.2 pA at 0 mV, suggesting a reversible fast blockade. Addition of increasing concentrations of inositol (1, 4, 5)-triphosphate (cis), increased P0 from 0.10 +/- 0.01 (mean +/- SEM) in the control to 0.85 +/- 0.02 at 50 microM in an approximately sigmoidal fashion, with an apparent half-maximal activation at 15 microM inositol (1, 4, 5)-trisphosphate in the presence of 40 microM cis Ca2+. Lower concentrations of this agonist were required to produce a significant increase in P0 when 10 microM or less cis Ca2+ were used. The channel was blocked by the addition to the cis compartment of either 0.5 mM lanthanum, 0.5 microM ruthenium red, or 200 nM ryanodine, all known inhibitors of Ca2+ release from sarcoplasmic reticulum vesicles. These results demonstrate the presence of calcium channels in the sarcoplasmic reticulum from frog skeletal muscle with a pharmacological profile consistent with a role in excitation contraction coupling and with the hypothesis that inositol ( 1,4,5)-trisphosphate is a physiological agonist in this process.