Evidence that prazosin disturbs isoprenaline positive inotropic action in the guinea pig heart papillary muscle.

The influence of prazosin (1-100 microM), known alpha 1-adrenoceptor blocking agent, on the contractility of guinea pig papillary muscle induced by noradrenaline and isoprenaline was studied. In the presence of prazosin (30 microM), the concentration-response curve for isoprenaline, known agonist of beta-adrenoceptor was strongly shifted to the right (about 17-fold). Additionally, the maximum positive inotropic effect of isoprenaline was significantly lower in comparison with that effect obtained without pretreatment with prazosin. The same concentration of prazosin attenuated the positive inotropic action of noradrenaline, known agonist of alpha- and beta 1-adrenoceptor, by about 17-fold, too. However, noradrenaline exerted the same maximum effect before and after pretreatment with prazosin. This findings suggest that prazosin, which is known alpha 1-blocker, can disturb beta-adrenoceptor signalling pathway in the guinea pig heart. The antagonistic effect of prazosin on isoprenaline induced positive inotropic action is nonspecific and uncompetitive. Taking into account the ability of prazosin to be accumulated in the heart muscle, coronary vessels, lung and some other tissue, the relatively high concentration of prazosin (30 microM), which is necessary for aformentioned effect, could be reached. However, further investigations are required to clarify the precise mechanism involved in this phenomenon.