High-dose propranolol attenuates pressor responses to norepinephrine in mesenteric arterial beds of rats

Abstract

Propranolol is used for medical treatment of portal hypertension as it is believed to act as an indirect splanchnic vasoconstrictor via blockade of vasodilatory β₂-receptors. However, a high proportion of nonresponders have been demonstrated in hemodynamic studies of the portal hypotensive effect of propranolol. The aim of the present study was to investigate the effect of various concentrations of propranolol on norepinephrine-induced pressor responses in isolated perfused mesenteric arteries of rats. Mesenteric arterial beds of six rats were perfused at a constant rate of 2 ml/minute with Krebs-Ringer solution at 37°C, and perfusion pressure was continuously recorded. Pressor responses to bolus injections of norepinephrine tended to increase in the presence of 10⁻⁶ M propranolol but were significantly attenuated in the presence of 10⁻⁵ M propranolol. In conclusion, a high concentration of propranolol paradoxically attenuates the pressor responses to norepinephrine in mesenteric arterial beds of rats. This is most likely explained by a nonspecific local anesthetic effect of propranolol.