The possible participation of the nucleus reticularis gigantocellularis in the
hypotension, decrease in cardiac contractility and
bradycardia induced by
guanabenz was examined in rats that were anesthetized with
pentobarbital sodium (40 mg/kg, i.p.).
Guanabenz (10 micrograms/kg, i.v.) elicited an initial, transient
hypertension, accompanied by an increase in cardiac contractility, followed by a significant and sustained
hypotension, as well as decrease in the force and rate of cardiac contraction. In rats receiving bilateral focal electrolytic lesions of the nucleus reticularis gigantocellularis, the same injection produced only the initial transient responses, without the subsequent depressant effects. Microinjection of
guanabenz directly into the ventro-medial portion of the nucleus reticularis gigantocellularis, at an ineffective systemic concentration (500 ng), produced significant and prolonged reduction in arterial pressure, cardiac contractility and heart rhythm. On the other hand, local application of the same concentration (500 ng) of
guanabenz into the lateral portion of the same nucleus produced only minor
hypotension and
bradycardia, with no decrease in cardiac contractility. It is concluded that the nucleus reticularis gigantocellularis is at least one of the central sites through which
guanabenz may produce its cardiovascular suppressant effects.