Cardiac Depression Produced by L-Arginine and Phosphodiestrase Inhibitor on Isolated Mammalian Rabbit Heart: Function of Cyclic Guanosine Monophosphate (cGMP)

Abstract

Problem statement: Cyclic guanosine 3',5'-monophosphate cGMP is one the important second messengers that determines the cardiomyocyte activity and its role in healthy and diseased cardiac muscle is still controversial. We are reporting the effect of adding L-arginine, the NO donor that stimulates cGMP production and Sildenafil citrate (phosphodiestrase inhibitor) that inhibits cGMP hydrolyis on isolated rabbit’s heart to answer: Is it safe to prescribe phosphodiestrase inhibitors for men with low cardiac output? Approach: Isolated hearts from 6 rabbits were perfused using Langendorff’s apparatus in which the perfusion fluid was ringer-Locke solution, applied at constant flow rate and was continuously bubbled with a mixture of 95% oxygen and 5% carbon dioxide. Each heart served as its own control before infusion of L-arginine in concentration of 3 m mol L⁻¹ and Sildenafil citrate 1.5 mg L⁻¹ simultaneously. Their effects were recorded after 1, 3, 5 and 10 min. The effluent fluid was collected for cardiac enzymes assay after 5 and 10 min. Results: Data showed that the infusion of L-arginine and Sildenafil citrate produced negative inotrpic and chronotropic effects. Also, the cardiac enzymes were significantly elevated. Conclusion: The present study, which was carried out on the isolated rabbit’s heart, demonstrated that increased cGMP could produce a cardioprotective role by decreasing the cardiac work, although it might be hazardous to men with depressed cardiac function.