PROLONGED CENTRAL EFFECTS OF QUINPIROLE ON CARDIOVASCULAR REGULATION

Central cardiovascular effects of the dopamine D-2 receptor agonist qu inpirole were studied in conscious rats. The i.v. injection of 0.3 mg/ kg of quinpirole in spontaneously hypertensive rats (SHR) caused a rap id but short-lasting increase in blood pressure. Heart rate showed lit tle change. Pretreatment with the centrally acting selective dopamine D-2 receptor antagonist raclopride, but not the D-1 antagonist SCH2339 0, completely prevented the rise in blood pressure. A second injection of quinpirole, 30 min after the first injection, induced little chang e in blood pressure, although at 4 or 24 hr after quinpirole treatment , we observed partial and complete recovery of the presser response, r espectively. This pattern of desensitization was similar to that seen after administration of the dopamine D-2 receptor agonists N-propylnor apomorphine (0.3 mg/kg) or quinelorane (0.1 mg/kg), and was similar in spontaneously hypertensive rats, Wistar Kyoto and Sprague-Dawley rats . At 30 min after treatment with quinpirole, the hypotension induced b y i.v. injection of clonidine (0.01 mg/kg) or of 8-hydroxy-dipropylami notetralin (0.1 mg/kg) was markedly reduced when compared to that in s aline-pretreated spontaneously hypertensive rats, suggesting a prolong ed effect of quinpirole at the level of sympathetic regulation. The ra pid fall in blood pressure caused by i,v. injection of the ganglion bl ocker pentolinium (10 mg/kg) was slightly, but significantly enhanced by treatment with quinpirole, which suggests an overall prolonged incr ease in resting sympathetic vasomotor tone. This would be difficult to reconcile with an inhibition of the action of sympatholytic drugs, un less it is hypothesized that the increase in sympathetic vasomotor ton e was differential between different sympathetic beds or different neu ronal populations in the brain. This may prohibit any additional press er responses and, through a central feedback mechanism, may inhibit th e action of sympatholytic drugs. No evidence was found for lasting cha nges in circulating levels of vasopressin, angiotensin or atrial natri uretic factor, nor were there changes in hematocrit. Cardiac sympathet ic tone appeared to be enhanced, although vagal tone was normal and no major changes in baroreflex sensitivity were observed.