ENDOTHELIAL FUNCTION IN DEOXYCORTICOSTERONE NACL HYPERTENSION - EFFECT OF CALCIUM SUPPLEMENTATION

Background Dietary calcium intake has been suggested to correlate inve rsely with blood pressure in humans and experimental animals. However, the effects of calcium supplementation on hypertensive disturbances o f the endothelium have nor been well characterized. Methods and Result s Wistar-Kyoto rats were made hypertensive by deoxycorticosterone (DOC )-NaCl treatment, but a concurrent increase in chow calcium content fr om 1.1% to 2.5% markedly attenuated the rise in blood pressure. The fu nction of isolated mesenteric arterial rings in vitro was investigated at the close of the 10-week study. In norepinephrine-precontracted ri ngs, the relaxations to acetylcholine (ACh) and ADP, as well as to nit roprusside, 3-morpholinosydnonimine, and isoploterenol were attenuated in hypertensive rats on 1.1% calcium, but these responses were improv ed by calcium supplementation. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), the relaxations to ACh in hypertensive animals on normal calcium were practically absent, whereas in normotensive rat s and calcium-supplemented hypertensive rats, distinct relaxations to higher concentrations of ACh were still present. These responses were reduced by 30% to 50% with apamin, a blocker of Ca2+-activated K+ chan nels, and were further inhibited by blockade of ATP-dependent K+ chann els with glyburide. Interestingly, relaxations elicited by ACh and ADP during precontraction with 60 mmol/L KCl (preventing endothelium-depe ndent hyperpolarization) were not impaired in hypertensive animals. Th e contractile sensitivity of endothelium-intact arterial rings to 5-hy droxytryptamine and norepinephrine was higher in hypertensive rats on either normal or high-calcium diet, whereas the increase in contractil e sensitivity caused by L-NAME corresponded in all groups. Conclusions High-calcium diet markedly opposed experimental DOC-NaCl hypertension , an effect associated with improved arterial relaxation, while abnorm alities of vascular contractile properties remained unaffected. In par ticular, the hyperpolarization-related component of endothelium-depend ent arterial relaxation, mediated via opening of arterial K+ channels, could be augmented by calcium supplementation in DOC-NaCl hypertensio n.