Renal responses to intra-arterial administration of adrenomedullin in dogs.
The present study was undertaken to evaluate the renal responses to intra-arterial infusion (12.5 pmol.kg-1.min-1) for 30 min of adrenomedullin (ADM) in denervated kidneys of anesthetized dogs (n = 8). Total renal blood flow (RBF) was measured with an electromagnetic flow probe, and two single-fiber laser-Doppler needle flow probes were used to measure relative changes in cortical (CBF) and medullary blood flow (MBF). ADM administration resulted in decreases in renal vascular resistance (32.3 +/- 4.9 to 22.3 +/- 3.0 mmHg.ml-1.min.g) and increases in RBF (4.5 +/- 0.5 to 6.0 +/- 0.6 ml.min-1.g-1), CBF (33 +/- 1.3%, n = 41, and MBF (32 +/- 5.7%, n = 5) without changes in glomerular filtration rate. There were also substantial increases in urine flow (11.3 +/- 1.9 to 28 +/- 4.8 microliters.min-1.g-1), as well as in sodium excretion (1.8 +/- 0.2 to 4.2 +/- 0.6 microliter.min-1.g-1). After cessation of ADM infusion, partial recovery of these responses was observed within a 30-min period. Responses to ADM were attenuated during inhibition of nitric oxide (NO) synthesis by nitro-L-arginine (50 micrograms.kg-1.min-1). These findings indicate that renal vasodilator, diuretic, and natriuretic responses to ADM may be mediated by the release of endogenous NO and suggest that ADM could play a role in regulating water and electrolyte excretion by the kidney.
Majid
D S
DS
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Kadowitz
P J
PJ
Coy
D H
DH
Navar
L G
LG
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003714:Denervation; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D055590:Electromagnetic Phenomena; D007269:Injections, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D017078:Laser-Doppler Flowmetry; D009318:Natriuresis / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D010455:Peptides; D053607:Adrenomedullin; D019335:Nitroarginine; D019001:Nitric Oxide Synthase