HYPOTENSIVE ACTION OF BROMOCRIPTINE IN THE DOCA-SALT HYPERTENSIVE RAT- CONTRIBUTION OF SPINAL DOPAMINE-RECEPTORS

To assess the role of spinal dopamine receptors in mediation of hypote nsion induced by systemic administration of the dopamine D-2 receptor agonist, bromocriptine, conscious deoxycorticosterone acetate (DOCA)-s alt hypertensive rats were pretreated with either intravenous (iv; 500 mu g/kg) or intrathecal (it; 40 mu g/rat at T-9-T-10) domperidone, a selective dopamine D-2 receptor antagonist that does not cross the blo od-brain barrier. In DOCA-salt hypertensive rats, iv administration of a sub-maximal dose of bromocriptine (150 mu g/kg) induced a significa nt decrease in mean aortic pressure (MAP) which was greater and longer lasting than that in uninephrectomized control rats. Intravenous or i t pretreatment with domperidone reduced partially, but significantly, the hypotensive effect of bromocriptine (reduction of about 57% and 45 % of the maximal effect, respectively). The remaining responses observ ed during the 60 min postinjection period were still statistically sig nificant as compared with vehicle injection. In contrast, the bromocri ptine-induced hypotension was fully abolished by iv pretreatment with metoclopramide (300 mu g/kg), a dopamine D-2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with iv a nd it domperidone. These results suggest that, in DOCA-salt hypertensi ve rats, the hypotension induced by iv bromocriptine is mediated partl y through a peripheral D-2 dopaminergic mechanism and partly through s timulation of spinal dopamine D-2 receptors, as has been demonstrated in conscious normotensive rats. (C) Elsevier, Paris.