Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)