Androgen-Induced Enhancement of Vascular Reactivity

Abstract

Impairment of testosterone metabolism or excretion has been found in some patients with essential hypertension (Nowacynski et al. Can. J. Biochem. (1968), 46, 1031–1038). The effects of testosterone (10 mg/kg, intramuscular (i.m.)), methyltestosterone (10 mg/kg, i.m.), and vehicle on heart rate, arterial pressure, and responses of perfused canine hindpaws to intra-arterial norepinephrine (0.1–3.0 μg), tyramine (50 and 200 μg), angiotensin (0.1, 0.3, and 1.0 μg), and nitroglycerin (10 and 100 μg) were studied in three groups of dogs (five per group), 5 days after single doses of androgen or vehicle. Plasma and tibial artery electrolytes were also measured. After testosterone, heart rate (157 ± 5 beats/min) was higher than in control dogs after vehicle (132 ± 6 beats/min). Mean arterial pressure was similar in the two groups. Methyltestosterone-treated dogs had a significantly greater heart rate (160 ± 8 beats/min) than vehicle-treated animals. However, mean arterial pressures were similar in the two groups. A second series of dogs that received propranolol (1 mg/kg) 30 min before evaluation of heart rate showed no significant differences in heart rate among the treatment groups. Mean arterial pressures were similar in the three experimental groups. Pressor responses (expressed as the percentage change in perfusion pressure from the base line) to norepinephrine and tyramine were significantly enhanced after testosterone treatment. Pressor responses to angiotensin- and nitroglycerin-induced vasodilatation were unchanged after testosterone treatment when compared with vehicle controls. Pressor responses to tyramine, but not to norepinephrine, were also enhanced after methyltestosterone when compared with control responses after vehicle. Responses to angiotensin and nitroglycerin were similar in the two groups of animals. Plasma and tibial artery electrolytes were not different in the three experimental groups. These data suggest that single doses of androgen sensitized these animals to exogenously administered and endogenously released catecholamines. The effects were not mediated by sodium retention or altered plasma or tissue calcium concentrations.