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 hypotension induced by systemic administration of the dopamine D2 receptor agonist, bromocriptine, conscious deoxycorticosterone acetate (DOCA)-salt hypertensive rats were pretreated with either intravenous (i.v.; 500 micrograms/kg) or intrathecal (i.t.; 40 micrograms/rat at T9-T10) domperidone, a selective dopamine D2 receptor antagonist that does not cross the blood-brain barrier. In DOCA-salt hypertensive rats, i.v. administration of a sub-maximal dose of bromocriptine (150 micrograms/kg) induced a significant 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 observed during the 60 min postinjection period were still statistically significant as compared with vehicle injection. In contrast, the bromocriptine-induced hypotension was fully abolished by i.v. pretreatment with metoclopramide (300 micrograms/kg), a dopamine D2 receptor antagonist that crosses the blood-brain barrier, or by combined pretreatment with i.v. and i.t. domperidone. These results suggest that, in DOCA-salt hypertensive rats, the hypotension induced by i.v. bromocriptine is mediated partly through a peripheral D2 dopaminergic mechanism and partly through stimulation of spinal dopamine D2 receptors, has been demonstrated in conscious normotensive rats.