Effect of urapidil, clonidine, and prazosin on sympathetic tone in conscious rats.
To test the hypothesis that the hypotensive action of urapidil is in part related to a direct action on the brain, the central (intracerebroventricular) and peripheral (intravenous) effects of urapidil were studied and compared with those obtained with clonidine and prazosin. All studies were conducted in conscious, chronically instrumented stroke-prone spontaneously hypertensive rats (SHRSP). Efferent sympathetic nervous system activity was estimated by means of a bipolar electrode implanted on the splanchnic nerve. Only clonidine, administered intracerebroventricularly and intravenously, decreased sympathetic nerve activity. Urapidil and prazosin either did not affect sympathetic nerve activity after central administration or increased it after peripheral administration at low and high doses, respectively. Centrally administered urapidil and prazosin lowered blood pressure but also blocked the response to intravenously administered phenylephrine; this result suggests a peripheral effect. Centrally administered urapidil decreased heart rate. Urapidil given either intracerebroventricularly or into the cisterna magna had no influence on baroreceptor responses. Intravenous infusions of urapidil and prazosin in sufficient doses to lower blood pressure in spontaneously hypertensive rats by 50 mm Hg completely blocked the actions of phenylephrine. These data suggest that in conscious SHRSP urapidil lowers blood pressure through peripheral blockade of alpha 1-adrenergic receptors rather than by means of central sympathetic suppression. In this regard urapidil resembles prazosin rather than clonidine; however, the effect of urapidil on heart rate is consistent with a central mode of action.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004566:Electrodes; D006339:Heart Rate / Q000187:drug effects; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D013153:Splanchnic Nerves / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*
D010879:Piperazines; C015568:urapidil; D003000:Clonidine; D011224:Prazosin