Nitric oxide inhibits the positive chronotropic and inotropic responses tosympathetic nerve stimulation in the isolated guinea-pig atria

This study was designed to determine whether nitric oxide (NO) modulates th e positive chronotropic and inotropic tin paced atria) responses to cardiac sympathetic nerve stimulation (SNS) in the isolated guinea-pig double atri al/right stellate ganglion preparation. The ganglion was stimulated at 1, 2 , 3 and 5 Hz at constant voltage and the changes in heart rate or force of contraction were measured. The selective neuronal NO synthase (nNOS) inhibi tors TRIM(1-(2-trifluoromethylphenyl) imidazole; 100 mu M) and 7-NiNa (Nasalt of 7-nitroindazole: 100 mu M) significantly enhanced the positive chro notropic and inotropic responses to SNS. Similar results for heart rate wer e seen with the non-isoform-selective NOS inhibitor N omega nitro-L-arginin e (L-NA; 100 mu M) all effects were reversed with L-arginine (I mM). The NO donor sodium nitroprusside (SNP: 100 mu M) increased baseline heart rate a nd force of contraction, and attenuated the positive chronotropic and inotr opic responses to SNS. SNP also decreased the positive chronotropic respons e to bath-applied noradrenaline(NA: 1 mu M) In contrast, 7-NiNa did not alt er the increase in heart rate with bath-applied NA (0.1 or 1 mu M). The gua nylyl cyclase inhibitor ODQ (10 mu M) enhanced (mimicking nNOS inhibition) and the cyclic GMP (guanosine 3':5'-cyclic monophosphate) analogue 8-Br-cGM P (8-bromoguanosine 3':5'-cyclic monophosphate: 1 mM) attenuated (mimicking exogenous NO) the positive inotropic response to SNS. Taken together, thes e results rue consistent with endogenous NO, synthesized from nNOS, inhibit ing the positive chronotropic and inotropic responses evoked by cardiac SNS via a cyclic GMP-dependent pathway. (C) 1999 Elsevier Science B.V. All rig hts reserved.