Arterial Function in Experimental Hypertension. Influence of Dietary Potassium and Exercise

Abstract

This study was designed to examine arterial function in three different models of experimental hypertension, and study the influences of Whey supplementation, increased dietary K+ intake, and regular physical exercise on the control of arterial tone in experimental hypertension.

The major findings and conclusions are: 1. Experimental models of genetic, mineralocorticoid-NaCl-induced, and obesity-related hypertension were associated with attenuated arterial dilatation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-NO pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle of SHR and DOC-treated animals, while such an abnormality was not observed in obesity-related hypertension. 2. Supplementation with Whey and a comparable dose of K+ similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Supplementation with Whey had a protective effect on endothelium-mediated control of arterial tone in experimental DOC-NaCl hypertension even in the absence of a significant effect on blood pressure. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to NO, and decreased the production of vasoconstrictor prostanoids. Altogether the beneficial effects of the Whey diet could be attributed to increased intake of K+ in SHR and DOC. 3. The antihypertensive effect of long-term exercise in experimental obesity-related hypertension was associated with improved vasodilation. This was expressed as enhanced relaxation via endogenous and exogenous NO, and increased endothelial PGI2 production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected. 4. The sensitivity of NOS to induction by IL-1ß was higher in arterial smooth muscle of the OZR than the lean controls. Thus, this model of hyperinsuli-naemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1ß. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both rats strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1ß. 5. In the absence of preceding myocardial hypertrophy the long-term exercise-induced workload was not deleterious to the heart in experimental OZR, since no changes in plasma and tissue atrial natriuretic peptide were detected.

This study was designed to examine arterial function in three different models of experimental hypertension, and study the influences of Whey supplementation, increased dietary K+ intake, and regular physical exercise on the control of arterial tone in experimental hypertension.

The major findings and conclusions are: 1. Experimental models of genetic, mineralocorticoid-NaCl-induced, and obesity-related hypertension were associated with attenuated arterial dilatation. The defect of endothelium-mediated relaxation most likely resulted from impaired endothelium-dependent hyperpolarization of vascular smooth muscle in these hypertensive models, whereas the endothelial L-arginine-NO pathway appeared to be preserved. The function of voltage-dependent Ca2+ channels, as evaluated by enhanced inhibitory effect of nifedipine on the arterial contractions, was abnormal in smooth muscle of SHR and DOC-treated animals, while such an abnormality was not observed in obesity-related hypertension. 2. Supplementation with Whey and a comparable dose of K+ similarly opposed the development of experimental genetic hypertension, an effect which was associated with improved arterial dilatory properties. Supplementation with Whey had a protective effect on endothelium-mediated control of arterial tone in experimental DOC-NaCl hypertension even in the absence of a significant effect on blood pressure. Both supplements augmented the hyperpolarization-related component of arterial relaxation, increased the sensitivity of smooth muscle to NO, and decreased the production of vasoconstrictor prostanoids. Altogether the beneficial effects of the Whey diet could be attributed to increased intake of K+ in SHR and DOC. 3. The antihypertensive effect of long-term exercise in experimental obesity-related hypertension was associated with improved vasodilation. This was expressed as enhanced relaxation via endogenous and exogenous NO, and increased endothelial PGI2 production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected. 4. The sensitivity of NOS to induction by IL-1ß was higher in arterial smooth muscle of the OZR than the lean controls. Thus, this model of hyperinsuli-naemia was not associated with reduced sensitivity of smooth muscle NOS to induction by IL-1ß. Regular exercise did not change plasma insulin concentrations, but it enhanced the action of insulin in both rats strains as reflected by reduced blood glucose, and increased the sensitivity of smooth muscle NOS to induction by IL-1ß. 5. In the absence of preceding myocardial hypertrophy the long-term exercise-induced workload was not deleterious to the heart in experimental OZR, since no changes in plasma and tissue atrial natriuretic peptide were detected.