Head G A, Burke S L
Neuropharmacology Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
J Hypertens. 1998 Apr;16(4):503-17. doi: 10.1097/00004872-199816040-00012.
To determine the contribution of the rostral ventrolateral medulla and the nucleus of the solitary tract in mediating the attenuation of the renal sympathetic baroreflex produced by administration of rilmenidine to anaesthetized rabbits and to examine the relative contribution of alpha2-adrenoceptors and imidazoline receptors at these sites to the cardiovascular effects of rilmenidine.
Rilmenidine micro-injected into the rostral ventrolateral medulla produced hypotension and inhibition of renal sympathetic nerve activity with doses an order of magnitude lower than those required in the nucleus tractus solitarius. Alpha-methylnoradrenaline, however, was similarly potent at producing hypotension when it was injected into the rostral ventrolateral medulla or nucleus tractus solitarius but, unlike rilmenidine, did not lower renal sympathetic nerve activity when it was injected into the nucleus tractus solitarius. The alpha2-adrenoceptor antagonist 2-methoxyidazoxan partially reversed the hypotension and renal sympathetic nerve activity inhibition due to alpha-methylnoradrenaline when it was administered into the rostral ventrolateral medulla, whereas the mixed alpha2-adrenoceptor/imidazoline receptor antagonists, idazoxan and efaroxan, did not. 2-Methoxyidazoxan, but not idazoxan, also reversed the hypotension when alpha-methylnoradrenaline was administered into the nucleus tractus solitarius. The hypotension induced by rilmenidine in the rostral ventrolateral medulla was completely reversed both by 2-methoxyidazoxan and by idazoxan, as was the sympathetic inhibition. To assess any interaction between the nucleus tractus solitarius and the rostral ventrolateral medulla in mediating the baroreflex effects of rilmenidine, we injected rilmenidine into the rostral ventrolateral medulla, the nucleus tractus solitarius or both nuclei and determined renal baroreflex responses of sympathetic nerve activity using drug-induced changes in blood pressure. Injection of 0.5 nmol rilmenidine into the rostral ventrolateral medulla reduced mean arterial pressure and basal renal sympathetic nerve activity as well as renal sympathetic baroreflex range (by 27%) and gain (by 35%). In contrast, injection of rilmenidine into the nucleus tractus solitarius had no effect on basal renal sympathetic nerve activity and renal sympathetic baroreflex parameters. The effect of combined injection was similar to that of administration into the rostral ventrolateral medulla alone.
Our results show that the rostral ventrolateral medulla, rather than the nucleus tractus solitarius, is the major site involved in the hypotension and inhibition of the renal sympathetic baroreflex by rilmenidine. Comparison of the actions of alpha2-adrenoceptor and imidazoline receptor antagonists on the effects of rilmenidine and alpha-methylnoradrenaline suggests that these agents are acting at different receptors, presumably imidazoline and alpha2-adrenoceptors receptors, respectively, and that both are important in lowering sympathetic tone and blood pressure in the rostral ventrolateral medulla.
确定延髓头端腹外侧区和孤束核在介导利美尼定对麻醉兔肾交感压力反射的减弱作用中的贡献，并研究这些部位的α2-肾上腺素能受体和咪唑啉受体对利美尼定心血管效应的相对贡献。
将利美尼定微量注射到延髓头端腹外侧区可产生低血压并抑制肾交感神经活动，所需剂量比在孤束核中低一个数量级。然而，当将α-甲基去甲肾上腺素注射到延髓头端腹外侧区或孤束核时，产生低血压的效力相似，但与利美尼定不同的是，当将其注射到孤束核时并不会降低肾交感神经活动。当将α2-肾上腺素能受体拮抗剂2-甲氧基咪唑克生注射到延髓头端腹外侧区时，可部分逆转由α-甲基去甲肾上腺素引起的低血压和肾交感神经活动抑制，而混合的α2-肾上腺素能受体/咪唑啉受体拮抗剂咪唑克生和依酚氯铵则不能。当将α-甲基去甲肾上腺素注射到孤束核时，2-甲氧基咪唑克生而非咪唑克生也可逆转低血压。利美尼定在延髓头端腹外侧区诱导的低血压以及交感抑制均可被2-甲氧基咪唑克生和咪唑克生完全逆转。为评估孤束核和延髓头端腹外侧区在介导利美尼定压力反射效应中的相互作用，我们将利美尼定注射到延髓头端腹外侧区、孤束核或两个核团中，并利用药物诱导的血压变化来测定交感神经活动的肾压力反射反应。将0.5 nmol利美尼定注射到延髓头端腹外侧区可降低平均动脉压、基础肾交感神经活动以及肾交感压力反射范围（降低27%）和增益（降低35%）。相比之下，将利美尼定注射到孤束核对基础肾交感神经活动和肾交感压力反射参数没有影响。联合注射的效果与单独注射到延髓头端腹外侧区的效果相似。
我们的结果表明，延髓头端腹外侧区而非孤束核是利美尼定引起低血压和抑制肾交感压力反射的主要部位。比较α2-肾上腺素能受体和咪唑啉受体拮抗剂对利美尼定和α-甲基去甲肾上腺素作用的影响表明，这些药物作用于不同的受体，推测分别为咪唑啉受体和α2-肾上腺素能受体，且两者在降低延髓头端腹外侧区的交感张力和血压方面均很重要。
