Hypotensive Effects and Mechanisms of Adrenomedullin（13-52）

Adrenomedullin （AdM） is a newly isolated peptide with hypotensive activity in normotensive rats. Nothing has been known regarding its role in hypertensive animals. The functions of endogenous vasoconstrictive substances and endogenous vasorelaxant substances in controlling blood pressure have been understood in recent years. The interaction of AdM with these vasoactive substances is open to be clarified. The vasodilator effects of AdM and the C-terminal fragment of AdM,AdM （13-52）, were compared first and then the roles of AdM （13-52） in the blood pressure in the spontaneously hypertensive rat （SHR）,renal hypertensive rat （RHR） and control animals were observed. With isolated perfused aortic artery, the effects of AdM （13-52） on the release of endogenous vasoconstrictive peptides （angiotensin Ⅱ and endothelin）were studied.The relationship between the vasodilator effect of AdM （13-52）and the roles of prostacyclin or nitric oxide was studied in isolated aortic rings. Both AdM and AdM （13-52）had vasorelaxant effect. AdM （13-52） decreased blood pressure in hypertensive rats and control animals in a manner of dose-dependence and the hypotensive effect of AdM （13-52） on hypertensive rats was more potent than on normotensive rats. An antagonist for the receptor of calcitonin gene related peptide（CGRP） did not block the hypotensive effect of AdM （13-52）. In isolated perfused aortic artery,AdM （13-52 ） obviously inhibited the release of angiotensin Ⅱand endothelin. The vasodilator effect of AdM （13-52） partially or completely disappeared after the production of endogenous prostacyclin or nitric oxide was inhibited. AdM （13-52） has similar effect to AdM concerning vasodilation and the N-terminal fragment of AdM is not necessary for its cardiovascular function. The response of hypertensive rats to the hypotensive effect of AdM （13-52） is stronger than that of normotensive rats. It is possib1e that AdM is a newly identified endogenous antihypertensive peptide different from CGRP. The hypotensive mechanisms of AdM （13-52） in hypertensive rats might be related to the inhibition of excessive release of angiotensin Ⅱ and endothelin. The vasodilator effect of AdM depends on the existence of nitric oxide and /or prostacyclin.