Cardiovascular effects associated with antidiuretic activity of vasopressin after blockade of its vasoconstrictor action in dehydrated dogs.
In view of our previous findings that a specific antidiuretic (V2) agonist, 4-valine-8-D-arginine vasopressin, acutely increased cardiac output and heart rate in dogs, we examined the hypothesis that interaction with V2-like receptors might contribute to the hemodynamic response seen after blockade of the vasoconstrictor (V1) effect of arginine-vasopressin in dehydrated dogs. After 48 hours of water restriction which increased plasma vasopressin to 10.6 +/- 2.0 pg/ml, the V1 antagonist 1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid) 2-(O-methyl)tyrosine arginine-vasopressin, 10 micrograms/kg, was injected intravenously into six conscious dogs, and the combined V1 + V2 antagonist 1-(beta-mercapto-beta,beta,cyclopentamethylene propionic acid) 2-(O-ethyl)-D-tyrosine, 4-valine arginine-vasopressin, 10 micrograms/kg, was administered to another six dogs. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured before and 20-30 minutes after antagonist administration. Mean arterial pressure did not change significantly in either instance. Cardiac output increased by 31.0 +/- 7.1% after V1 blockade, but by only 10.8 +/- 2.1% following V1 + V2 blockade. Blood flow increased significantly and to a similar extent in the skin, the skeletal muscles, and the fat following both antagonists. Conversely, kidney, arterial liver, and bone blood flow increased only after V1 blockade. In six additional, normally hydrated conscious dogs, it was shown that the V1 + V2 antagonist had no significant hemodynamic effects, a finding previously established for the V1 antagonist. The V1 + V2 antagonist completely prevented the hemodynamic effects associated with administration of the V2 agonist 4-valine-8-D-arginine vasopressin, 200 ng/kg, whereas the V1 antagonist did not. Both antagonists had similar effects on the hemodynamic changes induced by nitroprusside infusion, namely a potentiation of the blood pressure lowering action. These results suggest that part of the hemodynamic response to blockade of the vasoconstrictor action of vasopressin in dehydration is caused by unmasking cardiovascular effects linked to the antidiuretic activity of the arginine-vasopressin molecule.
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001842:Bone and Bones / Q000098:blood supply; D002302:Cardiac Output / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D003681:Dehydration / Q000503:physiopathology*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply; D008099:Liver / Q000098:blood supply; D008297:Male; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D001127:Arginine Vasopressin; C016180:argipressin, Val(4)-; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C028884:1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin