Regulation of Cardiac Contractility and Glycolysis by Cyclic Nucleotides during Hypoxia
It has been suggested that cyclic nucleotides (cAMP and cGMP) participate in the regulation of cardiac contractility and glycolysis. In the present study, this possible involvement was examined in spontaneously beating rat atria during hypoxia (50% oxygen saturation). Thirty seconds after reduction of high oxygen saturation (HiOxSa) in the incubation medium, the contraction amplitude declined to 50% of the initial level. The decline was partly antagonized by norepinephrine (NE) or hypercalcemia. The cAMP level remained unchanged during hypoxia, but the cGMP content gradually increased. Paradoxically, the production of lactate decreased after 30 sec of hypoxia but had increased by 2 min, when depletion of creatine phosphate and ATP stores was also initiated. Sodium nitroprusside (nitroprusside) and NE elevated the cGMP and cAMP, respectively, in both HiOxSa and hypoxia. Nitroprusside and NE also showed a positive inotropic effect in HiOxSa. Verapamil decreased contractility without changing the levels of cAMP or cGMP. In HiOxSa, both nitroprusside and verapamil decreased lactate production but were not able to resist the increase in atrial lactate level brought about by NE. In hypercalcemia the amplitude increased, but lactate production was slightly reduced in HiOxSa. Between 5 and 10 min of hypoxia, 45Ca uptake was reduced to about one-third of that in the control. It is suggested that lack of oxygen has direct and parallel effects on the sarcolemma and the mitochondria. The former induces deterioration of contractility, the latter termination of aerobic energy production. Cyclic nucleotides are not involved in either of these phenomena. However, at a low rate of anaerobic glycolysis, e.g., in HiOxSa or at the very early stage of hypoxia, cGMP could inhibit and cAMP accelerate lactate production.
KeywordsSodium Nitroprusside Cyclic Nucleotide Lactate Production Creatine Phosphate Cardiac Contractility
Unable to display preview. Download preview PDF.
- 1.Abiko, Y., Ichihara, K., and Izumi, T. 1979. Effects of antianginal drugs on ischemic myocardial metabolism. In: M. M. Winbury and Y. Abiko (eds.), Perspectives in Cardiovascular Research, Vol. 3, pp. 155–169. Raven Press, New York.Google Scholar
- 11.Hohorst, H.-J. 1970. L-(+)-Lactat. Bestimmung mit Lactat-Dehydrogenase und NAD. In: H. U. Bergmeyer (ed.), Methoden der Enzymatischen Analyse II, pp. 1425–1429. Verlag Chemie, Weinheim.Google Scholar
- 13.Katz, A. M. 1977. Physiology of the Heart, pp. 420–428. Raven Press, New York.Google Scholar
- 16.Lambrecht, W., Stein, P., Heinz, F., and Weisser, H. 1970. Creatinphosphat. In: H. U. Bergmeyer (ed.), Methoden der Enzymatischen Analyse II, pp. 1729–1733. Verlag Chemie, Weinheim.Google Scholar
- 17.Lebedev, A. V., Levitsky, D. O., and Loginov, V. A. 1980. Lipid hydroperoxides as indicators of cation permeability through biological membranes (simplest calcium channel). J. Mol. Cell. Cardiol. 12(Suppl. 1):92.Google Scholar
- 20.Neely, J. R., Whitmer, K. M., and Mochizuki, S. 1976. Effects of mechanical activity and hormones on myocardial glucose and fatty acid utilization. Circ. Res. 38(Suppl. I):22–29.Google Scholar
- 22.Robison, G. A., Butcher, R. W., and Sutherland, E. W. 1971. Cyclic AMP. Academic Press, New York.Google Scholar
- 24.Tsien, R. W. 1977. Cyclic AMP and contractile activity in heart. Adv. Cycl. Nucl. Res. 9:363–420.Google Scholar