EFFECTS OF HIGH CALCIUM DIET ON ARTERIAL SMOOTH-MUSCLE FUNCTION AND ELECTROLYTE BALANCE IN MINERALOCORTICOID-SALT HYPERTENSIVE RATS

被引:27
作者
ARVOLA, P [1 ]
RUSKOAHO, H [1 ]
PORSTI, I [1 ]
机构
[1] UNIV OULU,DEPT PHARMACOL & TOXICOL,SF-90220 OULU,FINLAND
关键词
ARTERIAL SMOOTH MUSCLE; ATRIAL NATRIURETIC PEPTIDE; BLOOD PRESSURE; DIETARY CALCIUM; ELECTROLYTE BALANCE; INTRACELLULAR FREE CALCIUM; MINERALOCORTICOID-SALT HYPERTENSION;
D O I
10.1111/j.1476-5381.1993.tb13491.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The effects of a high calcium diet (2.5%) on blood pressure, electrolyte balance, plasma and tissue atrial natriuretic peptide (ANP), cytosolic free Ca2+ concentration ([Ca2+]i), and arterial smooth muscle responses were studied in one-kidney deoxycorticosterone (DOC)-NaCl hypertensive Wistar rats. 2 Calcium supplementation for 8 weeks markedly attenuated the development of DOC-NaCl hypertension and the associated cardiac hypertrophy, and prevented the DOC-NaCl-induced sodium-volume retention as judged by reduced plasma Na+, and decreased plasma and ventricular ANP concentrations in high calcium-fed DOC-NaCl rats. However, calcium supplementation did not affect the DOC-NaCl-induced rise in platelet [Ca2+]i. 3 Smooth muscle contractions of isolated mesenteric arterial rings in response to depolarization by K+ (20-30 mm) were enhanced in DOC-NaCl-treated rats, this enhancement being abolished by concurrent oral calcium loading. The Ca2+ entry blocker nifedipine (10 nm) inhibited the contractions induced by K+ (30-125 mm) more effectively in DOC-NaCl rats than in controls, while the inhibition in calcium-loaded DOC-NaCl rats was significantly greater than in controls only with 30 mM K+. 4 The contractions of mesenteric arterial rings induced by omission of K+ from the organ baths were used to evaluate cell membrane permeability to ions. In chemically denervated rings the onset of the gradual rise in contractile force in K+-free medium occurred earlier, and the rate of the contraction was faster in DOC-NaCl-treated rats than in controls and high calcium-fed DOC-NaCl rats. Smooth muscle relaxation induced by 0.5 mm K+ upon K+-free contractions was clearly slower in DOC-NaCl rats than in controls and calcium-supplemented DOC-NaCl rats. 5 The functions of arterial smooth muscle Na+, Ca2+ exchange and Ca2+-ATPase were evaluated by the aortic contractions elicited by low Na+ medium, and the subsequent relaxation responses induced by Ca2+-free solution (in the presence of 5 mm caffeine, 1 mum nifedipine and 10 mum phentolamine). The rate of aortic low Na+ contractions (evaluating Ca2+ influx via Na+, Ca2+ exchange), as well as that of subsequent relaxations was slower in DOC-NaCl-treated rats than in controls, whether the relaxation was induced in normal (144.Omm) or low (1.2 mM) organ bath Na+ concentration (reflecting Ca2+ extrusion by both Ca2+-ATPase and Na+, Ca2+ exchange, and by Ca2+-ATPase alone, respectively). However, in calcium-supplemented DOC-NaCl rats the aortic responses did not differ from control. The difference between the relaxation rate in normal and low Na+ concentration in each aortic ring, representing the contribution of Na+, Ca2+ exchange in these relaxations, was comparable in all groups. 6 In conclusion, calcium supplementation clearly attenuated the development of hypertension, cardiac hypertrophy, and sodium retention induced by the DOC-NaCl treatment. However, the associated rise in platelet [Ca2+]i was not prevented, suggesting that in this form of experimental hypertension increased dietary calcium does not lower blood pressure by reducing [Ca2+]i. The results from vascular responses in vitro suggest that in arterial smooth muscle the DOC-NaCl treatment increased contractile sensitivity to depolarization, voltage-dependent Ca2+ entry and cell membrane permeability to ions, and attenuated relaxation responses and vascular Na+, K+-ATPase function. The results further suggest reduced ability of the cell membrane to transport Ca2+(possibly via Ca2+-ATPase) in DOC-NaCl hypertension. The high calcium diet opposed these alterations. The present results thus provide evidence that the antihypertensive effect of a high calcium diet in mineralocorticoid-salt hypertension is mediated by its beneficial effects on systemic sodium balance and arterial smooth muscle function.
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页码:948 / 958
页数:11
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