Contribution of prostaglandins to the vasodepressor effect of dopamine in the rat

There is general agreement that the administration of dopamine causes reduction of blood pressure in d m a l s pre-treated with a-adrenoceptor blocking agents (Goldberg, 1972); this hypotensive response is thought to be due to vasodilatation of the renal, mesenteric and coeliac beds (Eble, 1964). Such a vasodepressor effect is not due to the stimulation of vascular j3-adrenoceptors, since ( f)-propranolol was not able to block it. Moreover, inability of pretreatment by reserpine, monoamine oxidase inhibitors, atropine or antihistamines to attenuate the vasodepressor action of dopamine, and specific antagonism for this &ect by several phenothiazines, haloperidol and other butyrophenones suggest that dopamine causes vasodilatation by an unusual mechanism: stimulation of specific vascular receptors (Goldberg, 1975). Nevertheless the release by dopamine of other vasodepressor agents, such as endogenous prostaglandins (PG) could also explain the depressor effect of the amine, since PG, and particularly PGA,, mimic some effects of dopamine. Based on this hypothesis, we investigated the effect ofindomethacin, a potent inhibitor of PG synthesis and release, on the vasodepressor action of dopamine in the anaesthetized rat pretreated by phenoxybenzamine. If the depressor response to dopamine is mediated by PG, then inhibition of PG synthesis and release may attenuate or abolish the response of the vascular bed to the amine. Seven male Sprague-Dawley rats (180-220 g) were anaesthetized with pentobarbitone (75 mg kg-l, i.p.). A carotid artery was catheterized for the measurement of mean arterial pressure via a Statham P23 D b pressure transducer connected with an MA83 electromanometer. Another catheter was introduced into a jugular vein for drug administration. The rats were first given phenoxybenzamine (6 mg kg-l, i.v.). Thereafter, the changes in mean arterial pressure induced by dopamine hydrochloride (25 , 50, 100 pg-l, i.v.) were studied before and -valuated 30 min after intravenous administration of hdomethacin ( 5 mg kg-l). In another experiment, blood pressure responses to Wchidonic acid (200 pg kg-l, i.v.), PGE, (5 pg kg-l, LV.1 and sodium nitroprusside (0.5 mg kg-l, i.v.) given @ a bolus, were measured in six anaesthetized rats preb t e d with phenoxybenzamine, before and 30 min lrter indomethacin. Dopamine hydrochloride produced a dose-dependent &depressor response in all rats; administration of indomethacin reduced the magnitude of this response (Table 1). As expected, arachidonic acid, PGE, and sodium nitroprusside also produced hypotensive effects. Indomethacin did not affect the depressor action of sodium nitroprusside, rather it enhanced the hypotensive effect of PGE, and fully reduced the vasodepressor action induced by arachidonic acid (Table 2).