Divergent effects of propranolol and nadolol in isolated mesenteric arteries from normal and portal hypertensive rats.

Propranolol, a non-selective beta-blocker, is used for treatment of portal hypertension as it is believed to diminish splanchnic blood flow both by reducing cardiac output (beta(1)-blockade) and by increasing splanchnic arteriolar resistance (beta(2)-blockade). However, possible vasodilatory properties of propranolol at higher concentrations may counteract splanchnic vasoconstriction. Nadolol, another nonselective beta-blocker, has also been suggested for treatment of portal hypertension. The aim of the present study was to investigate the effects of various concentrations of propranolol and nadolol on vascular resistance in isolated perfused mesenteric arterial beds from normal and portal hypertensive rats. At concentrations of 10(-7) mol L-1 to 10(-6) mol L-1 neither propranolol nor nadolol changed pressor responses to noradrenaline in normal rats. However, nadolol 10(-5) mol L-1 significantly increased, whereas propranolol 10(-5) mol L-1 reduced, noradrenaline-induced vasoconstriction both in normal and in portal hypertensive rats. This unexpected vasodilatory effect of propranolol at high concentrations was present in preparations stimulated by both noradrenaline and methoxamine but not vasopressin and thus may be due to competitive alpha-receptor blockade. In contrast, nadolol lacked this effect and produced splanchnic arteriolar vasoconstriction at high concentrations also.