Species differences in cardiovascular effects of a novel endogenous inotropic factor (EIF) isolated from porcine heart

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Paskvalin, Mario
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Species differences in the effects of an endogenous inotropic factor (EIF) were examined in isolated atria, trabeculae and aortic smooth muscle of guinea pig and rat. EIF was isolated and purified from porcine heart left ventricle. EIF produced a dose-dependent increase in contractile force in atria and right ventricle trabeculae of guinea pig and rat. The magnitude of the contractile effect, however, was significantly lower in both the tissues of rat as compared with guinea pig. In rat isolated aortic smooth muscle, EIF had no effect on the basal muscle tone. However, when isolated aortic rings were pre-contracted with 0.5[mu]M phenylephrine, EIF caused dose-dependent relaxation of the aortic smooth 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[mu]M phentolamine or 20[mu]M prazosin. On the other hand, when these same pre-treated rings were pre-contracted with histamine, before the addition of EIF, a dose-dependent EIF-induced relaxation of guinea pig aortic smooth muscle was observed. Depletion of catecholamines from the pre-synaptic nerve terminals innervating the aortic smooth muscle, with either 0.6mM rauwolscine or reserpine (5mg/Kg) given to guinea pig 24 hours before sacrificing the animal, completely prevented the EIF-induced contraction of aortic smooth muscle. Instead EIF caused a dose dependent relaxation of the histamine pre-contracted aortic smooth muscle similar to that observed in rat aortic smooth muscle rings. The relaxation effect of EIF was endothelium dependent and nitric oxide mediated in both species since EIF-induced relaxation could be inhibited by 2[mu]M L-NAME, a nitric oxide synthase inhibitor. Atropine (0.2[mu]M) or Indomethacin (10[mu]M) had no significant effect on EIF-induced relaxation of either guinea pig or rat aortic smooth muscle. These data demonstrate that EIF is a unique inotropic substance which may in addition to mechanical support reduce afterload by endothelium-dependent relaxation of aortic smooth muscle.