Objective: 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.
Methods and results: 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.
Conclusion: 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.