Effect of nitric oxide synthase inhibition on the sympatho-vagal control of heart rate

Claire E. Sears, Julia K. Choate, David J. Paterson

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48 Citations (Scopus)

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 (ΔHR 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-ω-nitro-l-arginine (l-NA, 50 mg kg-1 i.v.). Infusing isoprenaline (0.2 μg 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 N(G)-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 μM) 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. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)63-73
Number of pages11
JournalJournal of the Autonomic Nervous System
Volume73
Issue number1
DOIs
Publication statusPublished - 27 Aug 1998
Externally publishedYes

Keywords

  • Heart rate
  • Nitric oxide
  • Sympathetic
  • Vagal

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