Haemodynamic effects of massive doses of hydrocortisone and the interaction with phenoxybenzamine in controlled haemorrhagic shock in the dog.
Haemorrhagic shock was produced in anaesthetized dogs by bleeding into a blood reservoir system. The blood level of the reservoir was adjusted at a level above the heart, corresponding to a mean arterial blood pressure of 6.7 kPa (50 mm Hg). The dogs were treated with hydrocortisone and the adrenergic alpha-receptor blocking agent phenoxybenzamine during the hypotension period. Hydrocortisone (80-160 mg kg-1) was found to induce vasodilation, which, however, was of a very small magnitude and was of short duration. Phenoxybenzamine given after hydrocortisone caused very pronounced vasodilation. Hydrocortisone (80 mg kg-1) given after phenoxybenzamine also showed a vasodilator activity, which seemed to be greater than that of the same dose of hydrocortisone given alone. Thus, the vasodilator action of hydrocortisone does not seem to be due to an alpha-receptor blockade of the drug. The vasodilator action of phenoxybenzamine given after hydrocortisone was greater than that of even higher doses of the drug given alone. From the present findings and the fact that corticosteroids are known to potentiate the sympathomimetic action of catecholamines, it is suggested that the hydrocortisone-induced potentiation of the vasodilation action of phenoxybenzamine found is related to an increased vascular adrenergic beta-receptor tone.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010643:Phenoxybenzamine / Q000494:pharmacology*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects
D010643:Phenoxybenzamine; D010100:Oxygen; D006854:Hydrocortisone; D009638:Norepinephrine