NITRIC-OXIDE HAS NO CHRONOTROPIC EFFECT IN RIGHT ATRIA ISOLATED FROM RAT-HEART

This study was designed to determine if nitric oxide (NO) has direct e ffects on heart rate or if it is involved in the chronotropic actions of adrenergic or cholinergic stimulation. Right atria were isolated fr om hearts of adult male rats, bathed in Krebs-Henseleit buffer (37 deg rees C), and used to monitor spontaneous rate. For comparison, ring se gments of thoracic aorta were also suspended in the Krebs-Henseleit so lution and used to examine vascular actions of various agents. The dos e-dependent chronotropic effects of acetylcholine (10(-7)-10(-3) M) an d norepinephrine (10(-8)-3 x 10(-4) M) in right atria were not affecte d by pretreatment with 10(-4) M N-nitro-L-arginine or 10(-3) M N-nitro -L-arginine-methyl ester, inhibitors of L-arginide-derived NO producti on. SIN-1 (3-morpholino-sydnonimine), an agent which releases NO in aq ueous solution, elicited a dose-dependent (0.3-100 mu M) vasorelaxatio n in aortic preparations constricted with 60 mM KCl; the ED(50) value for this effect was increased by pretreatment with methylene blue (10 mu M) and LY-83,583 (6-(phenylamino)-5,8-quinolinedione; 1 and 3 mu M) , compounds which inhibit NO-induced stimulation of guanylate cyclase. SIN-1 produced a negative chronotropic effect in right atria; however , this action was not observed at concentrations less than 300 mu M an d was not antagonized by methylene blue or LY-83,583. 8-Bromo cyclic G MP produced a dose-dependent (10-3000 mu M) decrease in KCl-induced te nsion in aortic rings. In right atria, 8-bromo cyclic GMP elicited a p ositive chronotropic effect. These results suggest that NO has no chro notropic action in rat atrial preparations.