咪唑啉受体参与利美尼定对清醒家兔压力反射的作用。

Head G A, Burke S L, Sannajust F J

Neuropharmacology Laboratory, Baker Medical Research Institute, PO Box 6492 Melbourne, Victoria 8008, Australia.

J Hypertens. 2001 Sep;19(9):1615-24. doi: 10.1097/00004872-200109000-00014.

OBJECTIVE

It has been suggested that imidazoline receptors rather than alpha2-adrenoceptors are involved in the sympathoinhibitory action of centrally acting antihypertensive drugs such as rilmenidine. In the present study, we examined the relative importance of alpha2-adrenoceptors and imidazoline receptors in modulating the renal sympathetic and heart rate (HR) baroreflex in response to central administration of rilmenidine in conscious normotensive rabbits.

METHODS

In seven conscious rabbits, chronically instrumented with a fourth ventricular (4V) catheter, aortic and vena caval cuff occluders and a renal nerve electrode, we continuously recorded renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and HR and assessed baroreflex MAP-RSNA and MAP-HR relationships with balloon-induced ramp rises and falls in MAP. Rabbits were treated with 4V rilmenidine (22 microg/kg) followed by 4V idazoxan (30 microg/kg; a mixed alpha2-adrenoceptor and imidazoline receptor antagonist) or 4V 2-methoxy-idazoxan (1 microg/kg; an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors).

RESULTS

Rilmenidine lowered blood pressure by 24% and reduced both upper and lower plateaus of the renal sympathetic baroreflex curve, such that the RSNA range (difference between plateaus) was reduced by 40% (-32 +/- 10 normalized units). Curves were shifted to the left with the fall in MAP. Idazoxan restored MAP, maximum RSNA and the RSNA baroreflex range. By contrast the alpha2-adrenoceptor antagonist 2-methoxy-idazoxan caused only a partial recovery of MAP and RSNA baroreflex upper plateau and range (-9 +/- 2 mmHg, 29 and 33% lower than control). Both antagonists partially restored the HR baroreflex.

CONCLUSION

These findings suggest that in conscious rabbits, both imidazoline receptors and alpha2-adrenoceptors are involved in the central antihypertensive and baroreflex actions of rilmenidine, but that activation of imidazoline receptors is more important for its renal sympathoinhibitory action.

目的

有人提出，参与如利美尼定等中枢性抗高血压药物交感神经抑制作用的是咪唑啉受体而非α2-肾上腺素能受体。在本研究中，我们研究了α2-肾上腺素能受体和咪唑啉受体在调节清醒正常血压家兔中枢给予利美尼定后肾交感神经和心率（HR）压力反射中的相对重要性。

方法

在7只清醒家兔中，长期植入第四脑室（4V）导管、主动脉和腔静脉袖带阻断器以及肾神经电极，我们连续记录肾交感神经活动（RSNA）、平均动脉压（MAP）和HR，并通过球囊诱导的MAP斜坡上升和下降评估压力反射MAP-RSNA和MAP-HR关系。家兔先接受4V利美尼定（22微克/千克）治疗，随后接受4V伊达唑胺（30微克/千克；一种α2-肾上腺素能受体和咪唑啉受体混合拮抗剂）或4V 2-甲氧基-伊达唑胺（1微克/千克；一种对咪唑啉受体亲和力小的α2-肾上腺素能受体拮抗剂）治疗。

结果

利美尼定使血压降低24%，并降低了肾交感神经压力反射曲线的上下平台，使得RSNA范围（平台之间的差值）降低了40%（-32±10标准化单位）。随着MAP下降，曲线向左移动。伊达唑胺恢复了MAP、最大RSNA和RSNA压力反射范围。相比之下，α2-肾上腺素能受体拮抗剂2-甲氧基-伊达唑胺仅使MAP和RSNA压力反射上平台及范围部分恢复（比对照低-9±2毫米汞柱、29%和33%）。两种拮抗剂均使HR压力反射部分恢复。