Demonstration of an alpha adrenoceptor-mediated inotropic effect of norepinephrine in rabbit papillary muscle.

Other investigators have claimed that norepinephrine does not evoke a significant alpha adrenergic inotropic effect in rabbit ventricular myocardium in contrast to some other mammalian species, indicating an important functional limitation of the cardiac alpha adrenoceptors. We therefore characterized the inotropic effects of norepinephrine in isometrically contracting rabbit papillary muscles. We studied both contraction and relaxation by measuring developed tension and its first and second derivatives. Both the influence of propranolol and prazosin on concentration-effect curves of norepinephrine and the qualitative characteristics of the responses revealed that norepinephrine evoked both alpha and beta adrenergic inotropic effects. The alpha adrenergic response to norepinephrine was qualitatively markedly different from the beta adrenergic effect and qualitatively similar to the alpha adrenergic effect of phenylephrine which was also characterized for comparison. Although the alpha adrenergic response to norepinephrine was marked, the beta adrenergic effect was the dominating one when norepinephrine was administered alone. Thus, the beta adrenergic effect had to be extensively blocked to reveal the prazosin-sensitive alpha-1 adrenergic response. It is concluded that also in rabbit papillary muscles, norepinephrine evokes inotropic effects through both alpha and beta adrenoceptors.