CALCIUM SUPPLEMENTATION IS ASSOCIATED WITH ENDOTHELIUM-DEPENDENT ATTENUATION OF VASCULAR SMOOTH-MUSCLE REACTIVITY IN NORMOTENSIVE PREGNANT AND NONPREGNANT RATS

The study tests the hypothesis that the blood pressure lowering effect of a high calcium diet is mediated through attenuation of vascular re activity and examined the mechanisms involved in both normotensive pre gnant and nonpregnant rats. The contractile responses of aortic rings of Wistar rats fed on high (1.7%, 2.1%) and normal (0.9%) calcium diet s to phenylephrine, angiotensin II, KCl, and CaCl2 were studied. The r elaxations to acetylcholine and potassium chloride; as well as the eff ects of endothelial denudation, pretreatment with indomethacin (10(-6) mol/L), methylene blue (10(-6) mol/L), and calcium free solution on t he responses to phenylephrine were also examined. In both pregnant and nonpregnant rats, the contractile responses of aortic rings of animal s fed a high calcium diet to all the agents were significantly attenua ted, compared with those of controls, After endothelial denudation, or treatment with methylene blue, but not with indomethacin, the respons es of the rings to phenylephrine were enhanced and not different from similarly treated rings from rats on a normal calcium diet. There was no difference in the contractile responses to phenylpehrine in calcium free solution. The relaxation to acetylcholine, but not to potassium chloride, was enhanced in rings from rats on a high calcium diet. The diminution in reactivity was not associated with corresponding changes in sensitivity of the tissues. It is concluded that in normotensive r ats a high calcium diet is associated with diminished vascular smooth muscle reactivity that is endothelium dependent, and involves increase d stimulation of the nitric oxide-guanylate cyclase pathway but not of the sodium-potassium ATPase or prostacyclin. (C) 1998 American Journa l of Hypertension, Ltd.