Brain structures involved in the hypotensive effects of rilmenidine: evaluation by [14C]2-deoxyglucose autoradiography.
The centrally acting, antihypertensive drug rilmenidine has activity at both imidazoline-preferring receptors (IPRs) and alpha 2-adrenoceptors: the IPR has been proposed to be the predominant receptor responsible for the hypotensive effects of rilmenidine. In the present study, the neuroanatomic regions of the brain involved in mediating the hypotensive response to rilmenidine were investigated in spontaneously hypertensive rats with the use of [14C]2-deoxyglucose autoradiography. The selective alpha 2-adrenoceptor agonist B-HT 933 was also studied for comparison. Rilmenidine (1 mg/kg s.c.) and B-HT 933 (2 mg/kg s.c.) induced significant and similar reductions in mean arterial pressure (-24 +/- 2 and -18 +/- 5 mm Hg. respectively) and in heart rate (-62 +/- 29 and -69 +/- 14 beats/min. respectively), whereas the vehicle had no significant hemodynamic effects. [14C]2-Deoxyglucose autoradiography revealed significant reductions in glucose use in the following structures of rilmenidine-treated rats: intermediolateral cell column of the thoracic spinal cord, area postrema, ventrolateral medulla, nucleus tractus solitarius, and cuneate nucleus, B-HT 933 did not significantly influence glucose use in any neuroanatomic structure examined. These results provide support for the functional involvement of brainstem cardiovascular control centres and the involvement of IPRs in the hypotensive response to rilmenidine.
Macrae
I M
IM
Wellcome Surgical Institute, University of Glasgow, Scotland.
Browne
S E
SE
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001345:Autoradiography; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003847:Deoxyglucose / Q000032:analysis / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy; D054755:Imidazoline Receptors; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011955:Receptors, Drug / Q000187:drug effects; D000077769:Rilmenidine
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D001381:Azepines; D002250:Carbon Radioisotopes; D054755:Imidazoline Receptors; D010080:Oxazoles; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D003847:Deoxyglucose; C015603:azepexole; D005947:Glucose; D000077769:Rilmenidine