Role of I1 imidazoline receptors in the sympathoinhibition produced by intracisternally administered rilmenidine and moxonidine.

The role of alpha 2-adrenoceptors and I1 imidazoline receptors in the cardiovascular effects of rilmenidine (CAS 54187-04-1), moxonidine (CAS 75438-57-2) and guanabenz (CAS 23256-50-0) was studied in conscious rabbits. In radioligand binding studies, rilmenidine and moxonidine are selective for I1 imidazoline receptors (vs. alpha 2-adrenoceptors) and guanabenz is selective for alpha 2-adrenoceptors (vs. I1 imidazoline receptors). Efaroxan (CAS 89197-00-2; selective for I1 imidazoline receptors) and yohimbine (CAS 65-19-0; selective for alpha 2-adrenoceptors) were used as antagonists. All drugs were injected into the cisterna magna. Guanabenz (1, 3, 10 and 30 micrograms kg-1), rilmenidine (1, 3, 10 and 30 micrograms kg-1) and moxonidine (0.03, 0.1, 0.3 and 1 microgram kg-1) dose-dependently lowered blood pressure, heart rate and the plasma concentration of noradrenaline. In the antagonism experiments, guanabenz (10 micrograms kg-1), rilmenidine (10 micrograms kg-1) and moxonidine (0.3 micrograms kg-1) were administered first; they caused equal hypotension. Injection of the agonists was followed by injection of efaroxan (0.3-1 microgram kg-1) or yohimbine (0.1-0.3 micrograms kg-1). Efaroxan and yohimbine were equieffective at antagonizing the effects of guanabenz. In contrast, efaroxan was more effective than yohimbine at antagonizing the effects of rilmenidine and moxonidine. The results show that intracisternally administered guanabenz, rilmenidine and moxonidine cause sympathoinhibition. alpha 2-Adrenoceptors are responsible for the sympathoinhibition produced by guanabenz. In contrast, I1 imidazoline receptors are involved in the sympathoinhibition caused by rilmenidine and moxonidine.