Acute hemodynamic and renal effects of adrenomedullin in rats with aortocaval shunt.
Heart failure is characterized by increased vascular resistance and water retention. Adrenomedullin is a peptide hormone with vasodilating and diuretic properties whose efficacy in heart failure has not been well established. We used an aortocaval shunt model of moderate heart failure in rats and infused increasing doses of adrenomedullin, both as bolus injections and 20-min infusions. In controls, a clear dose-dependent 4.8+/-1.0 to 13.6+/-2.3 mm Hg decrease in arterial blood pressure was observed after injection of 1 microg to 30 microg of adrenomedullin. In rats with aortocaval shunt, the hypotensive responses were significantly diminished. The urine flow rate, which was diminished at baseline in rats with aortocaval shunt, was increased and normalized by adrenomedullin administration. The glomerular filtration rate increased after infusion of adrenomedullin (0.5 microg/kg min(-1)) from 2.37+/-0.25 to 3.47+/-0.43 ml/min (P<0.01) in controls and from 1.79+/-0.33 to 2.58+/-0.49 (P<0.05) in rats with aortocaval shunt. Similarly, renal blood flow was significantly increased by adrenomedullin in both groups. Our results indicate a beneficial effect of adrenomedullin on renal function in rats with aortocaval shunt. These data suggest that adrenomedullin might be of potential therapeutic value in heart failure, without inordinately decreasing blood pressure.
Willenbrock
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Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, University Hospital Charité, Humboldt University of Berlin, Germany. willenbrock@fvk-berlin.de
Pagel
I
I
Krause
E G
EG
Scheuermann
M
M
Dietz
R
R
D053607:Adrenomedullin; D000818:Animals; D001166:Arteriovenous Shunt, Surgical; D002316:Cardiotonic Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000652:urine; D006152:Cyclic GMP / Q000652:urine; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects
D002316:Cardiotonic Agents; D010455:Peptides; D053607:Adrenomedullin; D000242:Cyclic AMP; D006152:Cyclic GMP