Involvement of postsynaptic alpha 2-adrenoceptors and guanine nucleotide-binding protein in guanabenz-induced cardiovascular suppressant effects in the rat.
In adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium, pretreatment with the catecholamine-depleting agent, reserpine (150 micrograms, i.c.v.) significantly antagonized the hypotensive and negative inotropic and chronotropic effects of guanabenz, either given intravenously (100 micrograms/kg) or microinjected bilaterally (5 micrograms) into the nucleus reticularis gigantocellularis (NRGC), a medullary site of action for this centrally acting antihypertensive agent. Pretreating animals with microinjection of the selective norepinephrine neurotoxin, DSP4 (50 micrograms), into the bilateral NRGC, on the other hand, did not appreciably blunt the cardiovascular suppressive actions of the aminoguanidine compound. I.c.v. administration of pertussis toxin (2.5 micrograms), which potentially blocks the action of two guanine nucleotide-binding proteins (Gi and Go), significantly antagonized the circulatory inhibitory effects of guanabenz (100 micrograms/kg, i.v.). More specifically, this blocking effect was still apparent upon microinjecting pertussis toxin (250 ng) into the bilateral NRGC. These data suggest that both pre- and postsynaptic alpha 2-adrenoceptors, and a pertussis toxin sensitive G-protein(s) (Gi and/or Go), in the NRGC are crucial to the expression of the cardiovascular suppressant actions of guanabenz.
Chen
C H
CH
Department of Psychiatry, Veterans General Hospital, Taipei, Taiwan.
Chan
S H
SH
D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000502:physiology*; D006143:Guanabenz / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006830:Hydralazine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009200:Myocardial Contraction / Q000187:drug effects; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001596:Benzylamines; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D006830:Hydralazine; D012110:Reserpine; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D006143:Guanabenz; C012102:DSP 4