Differential patterns of local cerebral glucose utilisation associated with rilmenidine- or B-HT 933-induced hypotension.
The anti-hypertensive drug, rilmenidine, has activity at both imidazoline-preferring receptors (IPRs) and alpha 2-adrenoceptors. However, available evidence suggests that its hypotensive effect is mediated via central IPRs. In the present study, the neuroanatomical regions involved in mediating the hypotensive response to rilmenidine were investigated using the [14C]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 metabolic effects of rilmenidine were compared with those of B-HT 933, a selective, 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.). [14C]2-deoxyglucose autoradiography, initiated after stabilisation of the drug-induced reduction in blood pressure, revealed significant reductions (P < 0.05) in local cerebral glucose utilisation (LCGU) in 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-adrenoceptors such as nucleus accumbens, locus coeruleus, frontal cortex. 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 cardiovascular control centres in the central hypotensive effects of rilmenidine.(ABSTRACT TRUNCATED AT 250 WORDS)
Browne
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SE
Wellcome Surgical Institute, University of Glasgow, UK.
Macrae
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IM
D000818:Animals; D000959:Antihypertensive Agents; D001345:Autoradiography; D001381:Azepines; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007022:Hypotension / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D010080:Oxazoles; D051381:Rats; D011918:Rats, Inbred SHR; D000077769:Rilmenidine; D014018:Tissue Distribution
D000959:Antihypertensive Agents; D001381:Azepines; D010080:Oxazoles; C015603:azepexole; D005947:Glucose; D000077769:Rilmenidine