The importance of a central adrenergic mechanism in the cardiovascular responses to ouabain.
Central administration of ouabain in the ventricular system of vagotomized dogs and cats elicited increases in blood pressure, cardiac contractile force and cardiac rate followed by ventricular arrhythmia. Spinal transection (C2) or hexamethonium treatment abolished the central effects of ouabain. Bilateral stellate ganglionectomy prevented the tachycardia and reduced the pressor response to the lower dose (15 mug) of ouabain; bilateral adrenalectomy only reduced the pressor effect. Neither of the procedures alone was adequate to inhibit the cardiovascular responses following a higher dose (90 mug) of ouabain whereas a combination of both procedures blocked these responses completely. Tachyphylaxis to the cardiovascular effects of very high doses of intracerebroventricularly (i.c.v.)-administered ouabain was shown to be of central origin. Prior depletion of brain catecholamines by Ro 4-1284 or 6-hydroxy -dopamine, and central adrenergic neuron blockade by bretylium prevented the centrogenic effects of ouabain. Similarly, central alpha- or beta-adrenoceptor blockade also prevented the responses to i.c.v. orabain. The results suggest that ouabain causes the release of adrenergic mediator (noradrenaline) in the brain, probably by a depolarization of a primary neuron(s), and that the central adrenergic mechanism is responsible for the genesis of the cardiovascular effects. Both alpha- and beta-adrenoceptors seem to be important in the central control of cardiovascular function. The most sensitive site for ouabain action was found to be the posterior hypothalamus in the vicinity of the third ventricle.
D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002552:Cerebral Ventricles; D002818:Cordotomy; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007267:Injections; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology*; D013233:Stellate Ganglion / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014628:Vagotomy
D004246:Dimethylphenylpiperazinium Iodide; D010042:Ouabain