Endothelial potentiation of relaxation response to beta adrenoceptor blocking agents

A number of beta adrenergic blocking drugs were evaluated on ring preparations of endothelium intact and denuded segments of the rat aorta. The preparations were preconstricted under isometric conditions with an EC80 dose of phenylephrine. Labetalol (10(-7)-10(-5) M), MK-761 10(-7)-10(-5) M), timolol (10(-7)-10(-4) M) and propranolol (10(-6)-10(-4) M) relaxed both endothelium intact and denuded vessels in a dose-dependent manner. Spirendalol (2.8 X 10(-8)-8.1 X 10(-6) M), a specific beta-2 receptor antagonist and L643717 (1.8 X 10(-7)-3.6 X 10(-6) M), a specific beta-1 receptor antagonist did not elicit relaxation. Labetalol, MK-761, timolol and propranolol promoted relaxation only when vascular segments were preconstricted with phenylephrine or norepinephrine and failed to do so when prostaglandin F2 alpha or U46619 were used. This indicates a possible displacement of alpha adrenergic agonists with the beta antagonists. The degree of relaxation induced by labetalol, MK-761, timolol and propranolol was significantly less (P less than .05) when the endothelium was removed. Eicosatetraynoic acid (3.2 X 10(-5) M) significantly attenuated the relaxation response to labetalol, MK-761 and timolol in the intact but not in denuded vascular preparations. These studies suggest that some of the vascular effects of beta blockers may relate to the endothelium.