Central effects of quinpirole on blood pressure of spontaneously hypertensive rats.
The i.v. administration of the dopamine D-2 receptor agonist quinpirole induced a rapid increase in blood pressure in spontaneously hypertensive rats (SHR). Heart rate showed little change. The pressor response to quinpirole was similar in SHR and normotensive Wistar-Kyoto rats (WKY) at doses of 0.03 to 0.3 mg/kg but, at 1 mg/kg, quinpirole induced a greater increase in blood pressure in SHR than in WKY. In contrast, although both strains showed a decreased locomotor activity after administration of 0.01 to 0.05 mg/kg of quinpirole, only in WKY was activity enhanced by 0.25 to 1.25 mg/kg of quinpirole. The i.v. administration of the dopamine agonists apomorphine, N-propylnorapomorphine and (R)-(+)-3-(3-hydroxyphenyl)-N-propylpiperidine, but not the putative presynaptic D-2 agonist (S)-(-)-3-(3-hydroxyphenyl)-N- propylpiperidine, induced pressor responses in SHR comparable to those after quinpirole administration. The pressor effect of quinpirole was enhanced by pretreatment with the peripheral D-2 antagonist domperidone, but blocked by the centrally acting dopamine antagonists haloperidol or sulpiride. In SHR, which were pretreated centrally with pertussis toxin, quinpirole induced a significantly smaller increase in blood pressure than in control SHR. Pretreatment centrally with 6-hydroxydopamine had no effect on the pressor action of quinpirole in SHR. Thirty minutes after i.v. administration of quinpirole, an additional injection of quinpirole did not significantly change blood pressure. Increasing the interval between two subsequent injections of quinpirole showed that this desensitization slowly reversed, but only after 24 hr had the pressor response to quinpirole fully recovered.(ABSTRACT TRUNCATED AT 250 WORDS)
Marion Merrell Dow Research Institute, Strasbourg, France.
M
M
van den Buuse
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D037342:Pertussis Toxin; D019257:Quinpirole; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015259:Dopamine Agents; D018492:Dopamine Antagonists; D004873:Ergolines; D010566:Virulence Factors, Bordetella; D019257:Quinpirole; D037342:Pertussis Toxin