Species differences in the effects of an endogenous inotropic factor (EIF) on the myocardium and aortic smooth muscle

Possible species differences and organ specificity in contractile or relaxation effects of an endogenous inotropic factor (EIF) isolated and purified from porcine heart left ventricle were examined in guinea pig and rat isolated atria, trabeculae and aortic smooth muscle rings. EIF demonstrated a dose-dependent increase in contractile force in guinea pig and rat atria and right ventricle trabeculae. The magnitude of the contractile effect was significantly lower in both the preparations of rat species as compared with guinea pig. In rat isolated aortic rings, EIF had no effect on the basal muscle tone. However, when rings were pre-contracted with phenylephrine EIF caused dose-dependent relaxation of the muscle. When aortic rings isolated from guinea pig were used, EIF induced a dose-dependent contraction which could be blocked by pre-treating the rings with either 2 microM phentolamine or 20 microM prazosin. When these same pre-treated rings were pre-contracted with histamine before the addition of EIF, a dose-dependent relaxation of guinea pig aortic smooth muscle rings was observed. Also depletion of catecholamines from the pre-synaptic nerve terminals innervating the aortic rings, using either 0.6 mM rauwolscine or reserpinizing (5 mg/Kg) the guinea pig 24 hours before sacrificing the animal, completely prevented EIF-induced contraction of the aortic rings. Instead EIF caused a dose dependent relaxation of the histamine pre-contracted aortic rings similar to that observed in rat aortic rings. The relaxation effect of EIF was demonstrated to be endothelium dependent and nitric oxide mediated in both species since EIF-induced relaxation could be inhibited by 2 microM L-NAME, a nitric oxide synthase inhibitor. Atropine (0.2 microM) or Indomethacin (10 microM) had no significant effect on EIF-induced relaxation of either guinea pig or rat aortic smooth muscle.