van den Buuse M, Tritton S B, Burke S L, Head G A
Neuropharmacology Laboratory, Baker Medical Research Institute, Melbourne, Victoria, Australia.
J Auton Nerv Syst. 1998 Oct 15;72(2-3):187-94. doi: 10.1016/s0165-1838(98)00104-0.
Previous studies in conscious rats have shown that systemic administration of the dopamine D2 receptor agonist quinpirole causes a centrally-mediated increase in blood pressure which is associated with increased plasma levels of noradrenaline and adrenaline. In addition, treatment with quinpirole caused a marked inhibition of the antihypertensive effect of centrally-acting sympatho-inhibitory drugs such as clonidine, rilmenidine and alpha-methyldopa, suggesting an interaction at the level of sympathetic vasomotor tone. The main aim of the present study was investigate in conscious rabbits the effect of quinpirole on renal sympathetic nerve activity. In addition, we studied the effect of pretreatment with quinpirole on responses to additional quinpirole injections or rilmenidine treatment. Quinpirole treatment caused a prolonged dose-dependent increase in blood pressure and heart rate. Additional injection of quinpirole, 30 min after the first treatment, caused a significantly smaller pressor response (7+/-2 vs. 17+/-2 mm Hg). Injection of rilmenidine caused a larger decrease in blood pressure in rabbits which had been pretreated with quinpirole than in controls (-28+/-3 vs. -14+/-3 mm Hg). Total renal sympathetic nerve activity was markedly increased by quinpirole treatment (3.5-fold), an effect which could be attributed to both increased amplitude and increased frequency of the renal nerve signal. After a second injection of quinpirole, 30 min after the first treatment, only total renal sympathetic nerve activity and amplitude were increased and the effects were reduced. These results show marked actions of quinpirole on renal sympathetic nerve activity in conscious rabbits. However, the previously described apparent desensitisation to the antihypertensive effect of rilmenidine could not be observed in rabbits, suggesting marked species differences in the mechanism and site of action of rilmenidine.
以往对清醒大鼠的研究表明，全身给予多巴胺D2受体激动剂喹吡罗会引起中枢介导的血压升高，这与血浆去甲肾上腺素和肾上腺素水平升高有关。此外，喹吡罗治疗显著抑制了可乐定、利美尼定和α-甲基多巴等中枢作用的交感神经抑制药物的降压作用，提示在交感神经血管运动张力水平存在相互作用。本研究的主要目的是研究清醒兔中喹吡罗对肾交感神经活动的影响。此外，我们研究了喹吡罗预处理对再次注射喹吡罗或利美尼定治疗反应的影响。喹吡罗治疗导致血压和心率出现剂量依赖性的持续升高。首次治疗30分钟后再次注射喹吡罗，引起的升压反应明显较小（7±2 vs. 17±2 mmHg）。与对照组相比，注射利美尼定后，喹吡罗预处理的兔血压下降幅度更大（-28±3 vs. -14±3 mmHg）。喹吡罗治疗使肾交感神经总活动显著增加（3.5倍），这一效应可归因于肾神经信号的幅度增加和频率增加。首次治疗30分钟后再次注射喹吡罗，仅肾交感神经总活动和幅度增加，且效应减弱。这些结果表明喹吡罗对清醒兔的肾交感神经活动有显著作用。然而，但在兔中未观察到先前描述的对利美尼定降压作用的明显脱敏现象，提示利美尼定的作用机制和作用部位存在明显的种属差异。
