Quipazine increases renin release by a peripheral hemodynamic mechanism

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Neuroendocrinology

Background:

• Serotonin (5-HT) agonists are hypothesized to increase plasma renin activity (PRA) and arterial pressure (AP) through central mechanisms.
• Understanding the specific pathways involved in 5-HT-mediated cardiovascular regulation is crucial.

Purpose of the Study:

• To investigate the central versus peripheral actions of the serotonin agonist quipazine on hemodynamic parameters and plasma renin activity (PRA) in conscious rats.
• To differentiate the roles of central nervous system (CNS) and vascular 5-HT2 receptors in mediating the pressor and renin-releasing effects of quipazine.

Main Methods:

• Direct 5-HT agonist quipazine was administered intracerebroventricularly (i.c.v.) and intravenously (i.v.) to conscious male rats.
• Hemodynamic responses, including arterial pressure (AP) and renal blood flow (RBF), were measured.
• The effects of specific 5-HT2 receptor antagonists (LY 53857 and xylamidine) and other blockers (propranolol, prazosin, enalapril, V1-vasopressin antagonist) were assessed.

Main Results:

• Intravenous quipazine increased AP, PRA, and decreased RBF. Central administration of quipazine increased AP but not PRA.
• The increase in PRA by i.v. quipazine was not blocked by propranolol, indicating non-neural mechanisms.
• A CNS-penetrant 5-HT2 antagonist (LY 53857) blocked all responses to i.v. quipazine, while a peripheral antagonist (xylamidine) blocked renin and RBF responses but only attenuated the pressor response.

Conclusions:

• Quipazine increases AP through both central actions and peripheral vascular 5-HT2 receptor activation.
• The increase in PRA induced by systemic quipazine is secondary to renal hemodynamic changes and not mediated by central 5-HT pathways.
• Distinct roles for central and peripheral 5-HT2 receptors in mediating the cardiovascular and renin responses to quipazine were elucidated.