High-calcium diet enhances vasorelaxation in nitric oxide-deficient hypertension

Because the effects of calcium supplementation on arterial tone in nitric o xide-deficient hypertension are unknown, we investigated the influence of e levating dietary calcium from 1.1 to 3.0% in Wistar rats treated with N-G-n itro-L-arginine methyl ester (L-NAME; 20 mg.kg(-1).day(-1)) for 8 wk. A hig h-calcium diet attenuated the development of hypertension induced by L-NAME and abrogated the associated impairments of endothelium-independent mesent eric arterial relaxations to nitroprusside, isoproterenol, and cromakalim. Endothelium-dependent relaxations to acetylcholine during nitric oxide synt hase inhibition in vitro were decreased in L-NAME rats and improved by calc ium supplementation. The inhibition of cyclooxygenase by diclofenac augment ed the responses to acetylcholine in L-NAME rats but not in calcium + L-NAM E rats. When hyperpolarization of smooth muscle was prevented by KCl precon traction, the responses to acetylcholine during combined nitric oxide synth ase and cyclooxygenase inhibition were similar in all groups. Furthermore, superoxide dismutase enhanced the acetylcholine-induced relaxations in L-NA ME rats but not in calcium + L-NAME rats. In conclusion, calcium supplement ation reduced blood pressure during chronic nitric oxide synthase inhibitio n and abrogated the associated impairments in endothelium-dependent and -in dependent arterial relaxation. The augmented vasorelaxation after increased calcium intake in L-NAME hypertension may be explained by enhanced hyperpo larization and increased sensitivity to nitric oxide in arterial smooth mus cle and decreased vascular production of superoxide and vasoconstrictor pro stanoids.