Beneficial effect of amosulalol and phentolamine on post‐hypoxic recovery of contractile force and energy metabolism in rabbit hearts

Abstract

1 The effects of phentolamine, an ax-adrenoceptor blocking agent and amosulalol, an a1 and fadrenoceptor antagonist on hypoxia-induced impairment in cardiac function and metabolism were examined using the isolated heart Langendorff preparation of the rabbit. 2 Hypoxia induced cessation of cardiac contractile force, a rise in resting tension, a decrease in myocardial high-energy phosphates, an increase in tissue calcium content and the release of ATP metabolites from the heart. Subsequent reoxygenation resulted in little recovery of cardiac contractile force, and there were further increases in tissue calcium content and in the release of creatine kinase from the heart. 3 Treatment of hypoxic hearts with either 83 yM phentolamine or 45 gM amosulalol resulted in a suppression of the rise in resting tension, the tissue calcium accumulation and the release of creatine kinase and ATP metabolites during hypoxia. This treatment also elicited significant recovery of cardiac contractile force, restoration of myocardial high-energy phosphates, suppression of the release of creatine kinase and the accumulation of tissue calcium during reoxygenation. Both 83 Mm phentolamine and 45 Mm amosulalol exerted a significant prolongation of the effective refractory period of rabbit isolated atria.4 Lower concentrations of phentolamine (16jMm) and amosulalol (9 Mm), which are sufficient to exert an a-adrenoceptor blocking action, did not elicit an appreciable effect on the post-hypoxic recovery of cardiac contractile force. 5 These results suggest that phentolamine and amosulalol are capable of protecting the myocardium from hypoxia-induced derangements in cardiac function and metabolism. This effect is probably attributable to their membrane stabilizing effect, rather than to their a-adrenoceptor blocking action. IntroductionOxygen deficiency primarily induces functional and metabolic impairments in cardiac cells, which are believed to be dependent on the period and the severity of oxygen deficiency used (Hearse & Humphrey, 1975;Hearse et al., 1977;Nayler et al., 1979;Nayler, 1983;Murry et al., 1986;Allen & Orchard, 1987). Several investigators have demonstrated a cardioprotective action of both calcium antagonists (Fleckenstein, 1971; Aschraf & Kahamathra, 1984) and fI-adrenoceptor blocking agents in ischaemic hearts (Nayler et al., 1978b;Wrangler et al. 1984). We have also shown that experimentally-induced hypoxic insults produce cardiac contractile failure, 1 Author for correspondence at present address: 1432-1, Horinouchi, Hachioji, Japan. impairments in myocardial energy metabolism and changes in cell membrane permeability, which can be prevented by diltiazem, verapamil (Takeo et al., 1988c) and coenzyme Q10 (Takeo et al., 1987). aAdrenoceptor blocking agents such as phentolamine and prazosin have been shown to be effective in protecting against post-ischaemic reperfusion-induced calcium accumulation in cat and rat hearts (Sharma et al., 1983;Nayler et al., 1985). This suggests that aand/or fi-adrenoceptor antagonists are...