NITRIC-OXIDE MODULATES SIGNALING BETWEEN CULTURED ADULT PERIPHERAL CARDIAC NEURONS AND CARDIOMYOCYTES

To determine whether nitric oxide (NO) modifies cardiomyocytes directl y or indirectly via peripheral autonomic neurons, the effects of NO we re studied in long-term (3-6 wk) cultures of adult guinea pig ventricu lar myocytes alone as well as in cocultures with adult extracardiac (s tellate ganglion) or intrinsic cardiac neurons. NADPH diaphorase was a ssociated histochemically with cultured intrinsic cardiac and, to a le sser extent, stellate ganglion neurons. The beating frequency of ventr icular myocytes cocultured with intrinsic cardiac neurons (M-intrinsic ) or stellate ganglion neurons (M-stellate) increased by 20-30% (P < 0 .001) after administration of the NO donor S-nitroso-N-acetylpenicilla mine (SNAP); this effect was abolished by the guanylate cyclase inhibi tor LY-83583. The beating frequency of noninnervated myocyte cultures was not affected by SNAP. The precursor of NO, L-arginine, also increa sed the beating rate (similar to 20%; P < 0.05) of M-intrinsic cocultu res, not affecting that of M-stellate cocultures or noninnervated myoc yte cultures. Augmentor effects induced by SNAP were no longer elicite d in the presence of tetrodotoxin and were unaffected by beta-adrenerg ic or muscarinic receptor blockade. It is concluded that 1) NO-sensiti ve neurons are present in stellate and intrinsic cardiac ganglia, and these neurons increase the beating rate of cardiomyocytes in the prese nce of NO; 2) more NO-synthesizing neurons are present in M-intrinsic than M-stellate cocultures, since L-arginine increased the beating fre quency of myocytes significantly only in M-intrinsic cocultures; and 3 ) the beating rate of noninnervated myocyte cultures is not directly a ffected by NO.