Quipazine increases renin release by a peripheral hemodynamic mechanism.
Systemically administered serotonin (5-HT) agonists have been suggested to act centrally to increase plasma renin activity (PRA) and arterial pressure (AP). To test this hypothesis, hemodynamic responses were determined in conscious male rats after intracerebroventricular (i.c.v.) or intravenous (i.v.) administration of the direct 5-HT agonist quipazine. When administered i.v., quipazine increased AP and PRA, and decreased renal blood flow (RBF); doses of quipazine i.c.v. that increased AP to a similar degree failed to increase PRA. The increase in PRA elicited by i.v. quipazine was not blocked by propranolol, suggesting non-neural mechanisms. The increase in AP and decrease in RBF elicited by i.v. quipazine were not eliminated by prazosin, enalapril, or a V1-vasopressin antagonist administered alone or in combination. LY 53857, a 5-HT2 antagonist that enters the central nervous system (CNS), blocked all responses to i.v. quipazine. In contrast, the peripheral 5-HT2 antagonist xylamidine blocked the renin and RBF responses, but only attenuated the pressor response to quipazine. These data suggest that quipazine can act in the CNS to increase AP, but when administered systemically quipazine also activates vascular 5-HT2 receptors to increase AP further and to decrease RBF. The increase in PRA caused by i.v. quipazine is secondary to renal hemodynamics and is unrelated to CNS actions of this drug.
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
M H
MH
Zink
P E
PE
Pergola
J F
JF
Doane
A F
AF
Sved
R H
RH
Alper
D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D011814:Quipazine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D011804:Quinolines; D012702:Serotonin Antagonists; D000804:Angiotensin II; D011814:Quipazine; D012083:Renin