Combination of ribose with calcium antagonist and beta-blocker treatment in closed-chest rats

Abstract

In previous studies ribose has been recognized as a substrate that has beneficial effects on myocardial metabolism. It leads to an elevation of the available 5-phosphoribosyl-1-pyrophosphate pool and stimulates adenine nucleotide de novo synthesis in the rat heart under control and various pathophysiological conditions (Zimmer and Gerlach, 1978; Zimmer and Ibel, 1983, 1984). When the clinical application of ribose in patients with heart disease is envisaged, it is understood that conventional cardiac therapy must be continued. It is therefore necessary to demonstrate in animal experiments that ribose retains its stimulating metabolic effect when administered in conjunction with therapeutically used drugs. In this study we have selected representatives of two pharmacological principles, the calcium antagonist verapamil and the beta 1-specific adrenoceptor blocker metoprolol. Measurements of functional parameters in closed-chest rats revealed that i.v. administration of ribose alone for 24 h (200 mg/kg/h) had no hemodynamic or vasoactive influence, whereas verapamil and metoprolol (i.v. infusion of 2 mg/kg/h each for 24 h) induced negative chronotropic and negative inotropic effects. Cardiac output was reduced by metoprolol, but not by verapamil. Ribose did not affect these drug-induced hemodynamic alterations, and verapamil as well as metoprolol did not interfere with the characteristic metabolic effect of ribose, the stimulation of cardiac adenine nucleotide de novo synthesis. Administration of ribose in combination with these pharmacological agents is therefore compatible.