Cardiovascular and renal effects of adrenomedullin in rats with heart failure.
Plasma adrenomedullin (AM), a novel hypotensive peptide, has been shown to increase in heart failure (HF). This study sought to examine the cardiovascular and renal effects of intravenous infusion of AM in HF rats and sham-operated rats (control) using two doses of AM that would not induce hypotension. Rat AM-(1-50) was intravenously administered at rates of 0.01 (low) and 0.05 (high) microg. kg body wt-1. min-1. Low-dose AM increased urine flow (+21% in HF, +29% in control) and urinary sodium excretion (+109% in HF, +123% in control) without changes in any hemodynamic variables. In contrast, high-dose AM slightly decreased mean arterial pressure (-3% in HF, -5% in control) and significantly increased cardiac output (+20% in HF, +12% in control). Infusion of high-dose AM resulted in significant decreases in right ventricular systolic pressure (-11%) and right atrial pressure (-28%) only in HF rats. High-dose AM significantly increased glomerular filtration rate (+10% in HF, +16% in control) and effective renal plasma flow (+25% in HF, +46% in control) as well as urine flow and urinary sodium excretion. In summary, intravenous infusion of AM exerted diuresis and natriuresis without inducing hypotension and, in the higher dose, produced beneficial hemodynamic and renal vasodilator effects in rats with compensated HF.
Nagaya
N
N
Department of Internal Medicine, National Cardiovascular Center, Suita, Osaka 565, Japan.
Nishikimi
T
T
Horio
T
T
Yoshihara
F
F
Kanazawa
A
A
Matsuo
H
H
Kangawa
K
K
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects; D002303:Cardiac Output, Low / Q000097:blood / Q000503:physiopathology*; D002319:Cardiovascular System / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D018377:Neurotransmitter Agents / Q000097:blood; D010455:Peptides / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects
D000959:Antihypertensive Agents; D018377:Neurotransmitter Agents; D010455:Peptides; D053607:Adrenomedullin