Pretreatment with quinpirole inhibits the central antihypertensive effects of rilmenidine and alpha-methyldopa in conscious rats.
Treatment of conscious spontaneously hypertensive rats (SHR) with the dopamine D2 receptor agonist quinpirole causes a short-lasting pressor response and apparent desensitisation to the effects of subsequent injections of quinpirole or central antihypertensives such as clonidine. In the present study, a number of aspects of this apparent desensitisation were investigated. Thirty minutes after intravenous injection of quinpirole into spontaneously hypertensive rats, treatment with the dopamine D2 receptors antagonist raclopride caused a significant fall in blood pressure. At this time point, circulating levels of vasopressin were not significantly different compared to controls. In Brattleboro rats, the pressor response to quinpirole was reduced in the first 15 min after injection, but not difference in blood pressure was observed at later time points. In SHR which had been treated with quinpirole, the central antihypertensive effects of rilmenidine or alpha-methyldopa were significantly inhibited. By contrast, the bradycardia induced by these drugs was similar in quinpirole-treated rats and controls. Quinpirole pretreatment caused an enhancement of the hypotension but a reduction of the reflex tachycardia after intravenous treatment with hydralazine. In SHR treated with methylatropine and quinpirole, the upper plateau of the sympathetic baroreceptor-heart rate reflex curve was reduced. These results show that treatment with quinpirole has marked effects on central sympathetic vasomotor mechanisms which are the target of antihypertensive drugs such as rilmenidine and alpha-methyldopa. At least some of these effects may occur at the level of the sympathetic baroreflex. Moreover, while the effects of quinpirole on sympathetic regulation are prolonged, the initial pressor response is counteracted by an as yet unidentified compensatory mechanism which can be unmasked when quinpirole is displaced from its receptor by dopamine D2 receptor antagonist treatment.
Van den Buuse
M
M
Baker Medical Research Institute, Prahran, Victoria, Australia. maarten.vandenbuuse@baker.edu.au
D000818:Animals; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors*; D004294:Domperidone / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D008750:Methyldopa / Q000037:antagonists & inhibitors*; D010080:Oxazoles / Q000037:antagonists & inhibitors*; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D000077769:Rilmenidine; D013045:Species Specificity; D014667:Vasopressins / Q000097:blood
D000959:Antihypertensive Agents; D018491:Dopamine Agonists; D010080:Oxazoles; D014667:Vasopressins; D019257:Quinpirole; D004294:Domperidone; D008750:Methyldopa; D000077769:Rilmenidine