Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 55; no. 6; pp. R1085 - R1092
• Main Authors: LUODONPÄÄ, Marja, LESKINEN, Hanna, ILVES, Mika, VUOLTEENAHO, Olli, RUSKOAHO, Heikki
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Physiological Society 01.06.2004
• Subjects: Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Circulatory system; Experimental diseases; Fundamental and applied biological sciences. Psychology; Hypertension; Medical sciences; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Peptides; Vertebrates: nervous system and sense organs; Heart; Hypertension; Systolic pressure; Cardiovascular control; catecholamines; Rat; Rodentia; ventricular function; Adrenomedullin; Cardiovascular disease; Catecholamine; Renin angiotensin system; Vertebrata; Mammalia; Animal; Norepinephrine; Blood pressure; Hemodynamics; Angiotensin II; Left ventricle performance; Hypertrophy
• ISSN: 0363-6119; 1522-1490

We examined whether adrenomedullin, a vasoactive peptide expressed in the heart, modulates the increase in blood pressure, changes in systolic and diastolic function, and left ventricular hypertrophy produced by long-term administration of ANG II or norepinephrine in rats. Subcutaneous administration of adrenomedullin for 1 wk inhibited the ANG II-induced increase in mean arterial pressure by 67% (P < 0.001) but had no effect of norepinephrine-induced hypertension. Adrenomedullin enhanced the ANG II-induced improvement in systolic function, resulting in a further 9% increase (P < 0.01) in the left ventricular ejection fraction and 19% increase (P < 0.05) in the left ventricular fractional shortening measured by echocardiography, meanwhile norepinephrine-induced changes in systolic function were remained unaffected. Adrenomedullin had no effect on ANG II- or norepinephrine-induced left ventricular hypertrophy or expression of hypertrophy-associated genes, including contractile protein and natriuretic peptide genes. The present study shows that adrenomedullin selectively suppressed the increase in blood pressure and augmented the improvement of systolic function induced by ANG II. Because adrenomedullin had no effects on ANG II- and norepinephrine-induced left ventricular hypertrophy, circulating adrenomedullin appears to act mainly as a regulator of vascular tone and cardiac function. [PUBLICATION ABSTRACT]