Hemodynamic effects of phenoxybenzamine in anesthetized dogs.
Our studies demonstrated that phenoxybenzamine, 10 mg/kg, administered intravenously to intact anesthetized dogs, produced an immediate and significant increase of heart rate and cardiac output. In heart-lung preparations, phenoxybenzamine had no effect or a negative cardiac inotropic effect, hence these actions were not related to direct cardiac action or to release of myocardial norepinephrine stores. Serial estimations of arterial blood catecholamines after phenoxybenzamine showed an increase of epinephrine and norepinephrine; the peak values of these catecholamines did not correlate well with the maximum cardiac output responses. Ganglionic blockade largely eliminated the early cardiac effects of phenoxybenzamine, hence its action did not appear to be upon peripheral terminals of postganglionic sympathetic or parasympathetic nerves. Phenoxybenzamine was found to have antivagal actions which might account for some of the delayed cardiac acceleration. When beta adrenergic receptor blockade was induced by sotalol, the cardiac effects of phenoxybenzamine were largely eliminated. Baroreceptor denervation prevented the increase of cardiac output after phenoxybenzamine. These observations are consistent with the concept that the increase of cardiac rate and output produced by phenoxybenzamine is principally mediated by baroreceptor reflexes acting through sympathetic cardiac nerves or circulating catecholamines.
D000311:Adrenal Glands / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002346:Carotid Sinus / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology; D002698:Chloralose; D004285:Dogs; D004837:Epinephrine / Q000378:metabolism; D005725:Ganglia, Autonomic / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006584:Hexamethonium Compounds; D007545:Isoproterenol / Q000494:pharmacology; D008722:Methods; D009020:Morphine; D009411:Nerve Endings; D009431:Neural Conduction; D009638:Norepinephrine / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology*; D011311:Pressoreceptors / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D006584:Hexamethonium Compounds; D010643:Phenoxybenzamine; D002698:Chloralose; D009020:Morphine; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine