Effects of renal medullary infusion of a vasopressin V1 agonist on renal antihypertensive mechanisms in rabbits.
The factors responsible for the development of hypertension during chronic activation of intrarenal V1 receptors are unknown. We therefore tested whether medullary interstitial infusion of the selective V1-receptor agonist [Phe2,Ile3,Orn8]vasopressin (V1 agonist) influences renal antihypertensive mechanisms initiated by increased renal perfusion pressure (RPP). In intact anesthetized rabbits, the V1 agonist (10 ng . kg-1 . min-1) reduced medullary perfusion by 36 +/- 7%, whereas cortical perfusion was reduced by only 14 +/- 2%. An extracorporeal circuit was used to increase RPP in a stepwise manner from 65 to 85, 110, 130, and 160 mmHg for consecutive 20-min periods. Increased RPP reduced mean arterial pressure by 35 +/- 8% in vehicle-treated rabbits, but by only 10 +/- 3% in V1 agonist-treated rabbits. Simultaneously, pressure-diuresis-natriuresis was induced; urine flow and sodium excretion increased similarly in the two groups of rabbits, but hematocrit did not change. We suggest that the depressor response to increased RPP is mainly due to release of a putative renal medullary depressor hormone (RMDH). Suppression of the release and/or actions of RMDH may therefore contribute to the hypertensive effect of chronic V1 receptor activation.
Department of Physiology, Monash University, Clayton, Victoria 3168, Australia.
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D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006706:Homeostasis; D006973:Hypertension / Q000517:prevention & control; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D007679:Kidney Medulla / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology*; D009951:Ornipressin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D017483:Receptors, Vasopressin / Q000819:agonists*; D012079:Renal Circulation / Q000187:drug effects
D017483:Receptors, Vasopressin; C082351:vasopressin, Phe(2)-Ile(3)-Orn(8)-; D009951:Ornipressin; D019335:Nitroarginine