Ce. Sears et al., EFFECT OF NITRIC-OXIDE SYNTHASE INHIBITION ON THE SYMPATHOVAGAL CONTROL OF HEART-RATE, Journal of the autonomic nervous system, 73(1), 1998, pp. 63-73
The role of nitric oxide (NO) in the sympatho-vagal control of heart r
ate was investigated in the cardiac sympathectomized and vagotomized a
naesthetised rabbit and in the isolated guinea-pig atria with intact v
agus nerve. Specific inhibition of neuronal nitric oxide synthase (nNO
S) with l-(2-trimethylphenyl) imidazole (TRIM, 50 mg kg(-1) i.v. in vi
vo) 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 revers
ed by L-arginine (Delta HR 37.2 +/- 4.1 bpm, 50 mg kg(-1) i.v.). An en
hanced 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.). Infusin
g isoprenaline (0.2 mu g kg(-1) min(-1)) did not mimic the change in H
R 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-N
MMA, 20 mg kg(-1) i.v.) on the magnitude of the change in HR with vaga
l nerve stimulation (5 Hz) in vivo. There was also no significant effe
ct of NOS inhibition on the change in HR with vagal nerve stimulation
in vivo in the presence of pre-adrenergic stimulation or in the presen
ce of propranolol (0.5 mg kg(-1) i.v., 2, 5 and 10 Hz stimulation). Th
is result was confirmed in the isolated guinea-pig atria with the spec
ific nNOS inhibitor, 7-nitroindazole (7-NiNa, 100 mu M) 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 endo
genous NO in vagal control of heart rate, with or without prior adrene
rgic stimulation. (C) 1998 Elsevier Science B.V. All rights reserved.