Cardiovascular responses to intrathecal dopamine receptor agonists in conscious DOCA-salt hypertensive rats

Previous studies have demonstrated that in conscious deoxycorticosterone ac etate (DOCA)-salt hypertensive rats, the hypotensive action of intravenous (i.v.) bromocriptine. a selective dopamine D-2 receptor agonist, was mediat ed partly by peripheral and partly by spinal dopamine D-2 receptor stimulat ion, and that this effect was greater and longer-lasting than that in unine phrectomized control rats. To determine whether this amplification results partly from a putative spinal hypersensitivity phenomenon, cardiovascular r esponses to intrathecal (i.t.) administration of apomorphine and quinpirole were studied in conscious, 4-week DOCA-salt hypertensive rats and compared with those in uninephrectomized control rats. In both groups, upper thorac ic (T-2-T-4) i.t. injections of apomorphine (9.1, 45.5 and 91.1 mu g/rat) i nduced immediate and dose-dependent decreases in mean aortic pressure (MAP) and heart rate (HR), while i.t. quinpirole (38.4 mu g/rat) induced only br adycardia. Neither magnitude nor duration of these responses was enhanced i n DOCA-salt hypertensive rats when compared to control rats. In DOCA-salt h ypertensive rats, apomorphine-induced hypotension and bradycardia remained unaffected by i.v. (500 mu g/kg) pretreatment with domperidone, a selective dopamine D-2 receptor antagonist that does not cross the blood-brain barri er. However, i.t. (40 mu g/rat at T-2-T-4) pretreatment with domperidone si gnificantly reduced apomorphine-induced hypotension, but fully suppressed b radycardia elicited by either apomorphine or quinpirole. These results demo nstrated that in conscious DOCA-salt hypertensive rats. intrathecally-injec ted apomorphine or quinpirole decreased MAP and/or HR through a spinal D-2 dopaminergic mechanism, as previously demonstrated in normotensive intact r ats. Since both magnitude and duration of these responses were unchanged wi th respect to uninephrectomized control rats. enhancement of the hypotensiv e effect of intravenously-administered bromocriptine in DOCA-salt hypertens ive rats does not appear to involve spinal dopamine D-2 receptors. (C) 1999 Editions scientifiques el medicales Elsevier SAS.