Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats.
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 (1.5 microg.kg(-1).h(-1)) for 1 wk inhibited the ANG II-induced (33.3 microg.kg(-1).h(-1) sc) increase in mean arterial pressure by 67% (P < 0.001) but had no effect of norepinephrine-induced (300 microg.kg(-1).h(-1) sc) 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.
Luodonpää
Marja
M
Department of Pharmacology and Toxicology, Biocenter Ouli, University of Oulu, 90014 Oulu, Finland.
Leskinen
Hanna
H
Ilves
Mika
M
Vuolteenaho
Olli
O
Ruskoaho
Heikki
H
D053607:Adrenomedullin; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004452:Echocardiography; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000517:prevention & control; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D058261:Receptor Activity-Modifying Proteins; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013686:Telemetry; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*; D014665:Vasodilator Agents / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010455:Peptides; D058261:Receptor Activity-Modifying Proteins; D044140:Receptor, Angiotensin, Type 1; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D053607:Adrenomedullin; D007703:Peptidyl-Dipeptidase A; D009638:Norepinephrine