Hemodynamic and renin responses to (+-)-DOI, a selective 5-HT2 receptor agonist, in conscious rats

The effect of the selective 5-HT2 agonist (+-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) on arterial pressure (AP), heart rate (HR), renal blood flow (RBF) and plasma renin activity (PRA) was determined in conscious rats. DOI increased AP and PRA, but decreased HR and RBF. All responses to DOI were abolished by central (LY 53857) or peripheral (xylamidine) 5-HT2 antagonists. Prazosin did not alter the AP or HR response to DOI. Chlorisondamine abolished the bradycardia but slightly increased the hypertension produced by DOI, while enalapril attenuated the pressor response. No further reduction was produced by the combination of enalapril and prazosin. Propranolol attenuated but did not eliminate the renin response, and blocked the bradycardia elicited by DOI. The data suggest that DOI activates 5-HT2 receptors located on vascular smooth muscle and/or the circumventricular organs of the brain to: (1) increase AP and reflexly decrease HR, (2) decrease RBF and (3) increase PRA. The hypertension is mediated by angiotensin II and direct vascular effects whereas the increase in PRA is mediated by an interaction of increased sympathetic nerve activity and decreased renal perfusion pressure.