DIFFERENTIAL PATTERNS OF LOCAL CEREBRAL GLUCOSE-UTILIZATION ASSOCIATED WITH RILMENIDINE- OR B-HT 933-INDUCED HYPOTENSION

The anti-hypertensive drug, rilmenidine, has activity at both imidazol ine-preferring receptors (IPRs) and alpha(2)-adrenoceptors. However, a vailable evidence suggests that its hypotensive effect is mediated via central IPRs. In the present study, the neuroanatomical regions invol ved in mediating the hypotensive response to rilmenidine were investig ated using the [C-14]2-deoxyglucose in vivo autoradiographic technique to map drug-induced changes in glucose utilisation within the CNS of conscious, spontaneously hypertensive rats (SHR). The cerebral metabol ic effects of rilmenidine were compared with those of B-HT 933, a sele ctive, alpha(2)-adrenoceptor agonist with no selectivity for the IPR. Rilmenidine (1 mg/kg, s.c.) and B-HT 933 (2 mg/kg, s.c.) both elicited a moderate but significant hypotension (-24 +/- 2 and -18 +/- 5 mmHg, resp.) and bradycardia (- 62 +/- 19.5 and - 69 +/- 14 beats/min, resp .). [C-14]2-deoxyglucose autoradiography, initiated after stabilisatio n of the drug-induced reduction in blood pressure, revealed significan t reductions (P < 0.05) in local cerebral glucose utilisation (LCGU) i n the intermediolateral cell column of the spinal cord, area postrema, ventrolateral medulla, nucleus tractus solitarius and cuneate nucleus of rilmenidine-treated rats. Rilmenidine did not significantly alter LCGU in a number of structures containing high densities of alpha(2)-a drenoceptors such as nucleus accumbens, locus coeruleus, frontal corte x. No significant changes in glucose use were evident in any of the 26 CNS regions examined following B-HT 933 administration. These results provide evidence for the functional involvement of brainstem cardiova scular control centres in the central hypotensive effects of rilmenidi ne. In addition, the neuroanatomical localisation of rilmenidine-induc ed glucose use changes in relation to the distributions of IPR and alp ha(2)-adrenoceptor binding sites, further supports the involvement of IPRs in the hypotensive response to rilmenidine.