Alpha-adrenoceptor blockade by tibalosine: hemodynamic and humoral effects at rest and during exercise, and effect of opioid receptor antagonism.

In a randomized double-blind protocol, 12 healthy male volunteers were studied twice at rest and during exercise after pretreatment for 1 week with placebo or 150 mg daily of the new alpha 1-adrenoceptor antagonist tibalosine. Six subjects received, on both experimental days, an intravenous infusion of saline and the other six received the opioid receptor antagonist naloxone. Combined measurements taken during rest and exercise showed tibalosine, on average, to decrease mean intraarterial pressure by 4.7 mm Hg and heart rate by 3.5 beats/min. Urinary volume and sodium excretion were transiently reduced by tibalosine as compared with placebo. Opioid antagonism by naloxone stimulated the pituitary-adrenal axis, but had no effect on the influence of tibalosine, as shown by hemodynamic, respiratory, and most humoral measurements. However, on interruption of exercise, opioid antagonism counteracted the inhibition of the plasma renin-angiotensin system by tibalosine, probably through the naloxone-induced increase in epinephrine release. In conclusion tibalosine reduced blood pressure at rest and during exercise independently of opioidergic mechanisms. This hypotensive action may be accompanied by sodium and fluid retention.