title: Effect of nitric oxide synthase inhibition on the sympatho-vagal contol of heart rate.
abstract: The role of nitric oxide (NO) in the sympatho-vagal control of heart rate was investigated in the cardiac sympathectomized and vagotomized anaesthetised rabbit and in the isolated guinea-pig atria with intact vagus nerve. Specific inhibition of neuronal nitric oxide synthase (nNOS) with 1-(2-trimethylphenyl) imidazole (TRIM, 50 mg kg(-1) i.v. in vivo) significantly enhanced the magnitude of the change in heart rate (HR) with sympathetic nerve stimulation (SNS, 31.6+/-4.5 bpm control vs. 49.7+/-6.0 bpm in TRIM, P < 0.05, 10 Hz). This effect was reversed by L-arginine (deltaHR 37.2+/-4.1 bpm, 50 mg kg(-1) i.v.). An enhanced HR response to SNS was also seen with the non-isoform specific inhibitor, N-omega-nitro-L-arginine (L-NA, 50 mg kg(-1) i.v.). Infusing isoprenaline (0.2 microg kg(-1) min(-1)) did not mimic the change in HR response to SNS with TRIM. There was, however, no significant effect of inhibition of NOS with TRIM L-NA or NG-monomethyl-L-arginine (L-NMMA, 20 mg kg(-1) i.v.) on the magnitude of the change in HR with vagal nerve stimulation (5 Hz) in vivo. There was also no significant effect of NOS inhibition on the change in HR with vagal nerve stimulation in vivo in the presence of pre-adrenergic stimulation or in the presence of propranolol (0.5 mg kg(-1) i.v., 2, 5 and 10 Hz stimulation). This result was confirmed in the isolated guinea-pig atria with the specific nNOS inhibitor, 7-nitroindazole (7-NiNa, 100 microM) at 1, 2, 3 or 5 Hz stimulation frequency. Our data suggest that endogenous NO plays an inhibitory role in cardiac sympathetic neurotransmission, but there was no convincing evidence from our results for a major role for endogenous NO in vagal control of heart rate, with or without prior adrenergic stimulation.
authors.affiliation: University Laboratory of Physiology, Oxford, UK. claire.sears@physiol.ox.ac.uk
authors.forename: C E
authors.initials: CE
authors.lastname: Sears
authors.forename: J K
authors.initials: JK
authors.lastname: Choate
authors.forename: D J
authors.initials: DJ
authors.lastname: Paterson
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000294:innervation; D006339:Heart Rate / Q000502:physiology*; D007191:Indazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D014630:Vagus Nerve / Q000187:drug effects / Q000201:enzymology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D011109:Polymethacrylic Acids; D013565:Sympatholytics; D013566:Sympathomimetics; D019335:Nitroarginine; D019323:omega-N-Methylarginine; C091347:vinyl ethyl methacrylate; D001120:Arginine; D011433:Propranolol; D019001:Nitric Oxide Synthase; D007545:Isoproterenol; C080122:7-nitroindazole