Comparative pathophysiological effects of methoxamine on arteriosclerotic vs. non-arteriosclerotic rats.

Methoxamine, a pure alpha-adrenergic stimulating agent, has little cardiac stimulating capacity but is a very potent vasoconstrictor. Currently, its clinical use is limited to correction of hypotensive crises during anaesthesia and surgical shock. A single injection of methoxamine will produce hypertension and marked medial arterial necrosis in animals. In this connection, we subjected arteriosclerotic and non-arteriosclerotic animals to a single injection of methoxamine and sacrificed the animals 4 hours, 2, 5 and 7 days later in order to determine whether the arteriosclerotic animals would differ from the non-arteriosclerotic animals in their response to the medial necrosis inducing effects of methoxamine. Within minutes after injection, the animals became prostrate, developed congestive heart failure and mortality was high. Myocardial infarction, adrenocortical haemorrhage and thymic, involution, intestinal gangrene as well as splenic, renal and testicular thrombosis and infarction were prevalent. Serum CPK, SGOT, glucose, triglyceride, free fatty acids, cholesterol, BUN and corticosterone manifested dynamic increases but the pattern of response was quite different in the arteriosclerotic non-arteriosclerotic animals. Although extensive medial necrosis was produced in the medium-sized arteries of animals with previously normal arteries, the damage was promptly repaired; the animals with pre-existing arteriosclerosis were not affected by the pressor effects of methoxamine. The induction of myocardial infarction, and extensive thrombosis and infarction are ascribed to the bradycardia-inducing effects of methoxamine and the medial necrosis-inducing effects are ascribed to its intense vasopressor activity.