Ce. Sears et al., INHIBITION OF NITRIC-OXIDE SYNTHASE SLOWS HEART-RATE RECOVERY FROM CHOLINERGIC ACTIVATION, Journal of applied physiology, 84(5), 1998, pp. 1596-1603
The role of nitric oxide (NO) in the cholinergic regulation of heart r
ate (HR) recovery from an aspect of simulated exercise was investigate
d in atria isolated from guinea pig to test the hypothesis that NO may
be involved in the cholinergic antagonism of the positive chronotropi
c response to adrenergic stimulation. Inhibition of NO synthesis with
N-G-monomethyl-L-arginine (L-NMMA: 100 mu M) significantly slowed the
time course of the reduction in HR without affecting the magnitude of
the response elicited by bath-applied ACh (100 nM) or vagal nerve stim
ulation (2 Hz). The half-times (t(1/2)) of responses were 3.99 +/- 0.4
1 s in control vs. 7.49 +/- 0.68 s in L-NMMA (P < 0.05). This was depe
ndent on prior adrenergic stimulation (norepinephrine, 1 mu M). The ef
fect of L-NMMA was reversed by L-arginine (1 mM; t(1/2) 4.62 +/- 0.39
s). The calcium-channel antagonist nifedipine (0.2 mu M) also slowed t
he kinetics of the reduction in HR caused by vagal nerve stimulation.
However, the t(1/2) for the reduction in HR with antagonists (2 mM Cs and 1 mu M ZD-7288) of the hyperpolarization-activated current were s
ignificantly faster compared with control. There was no additional eff
ect of L-NMA or L-NMMA + L-arginine on vagal stimulation in groups tre
ated with nifedipine, Cs+ Or ZD- 7288. We conclude that NO contributes
to the cholinergic antagonism of the positive cardiac chronotropic ef
fects of adrenergic stimulation by accelerating the HR response to vag
al stimulation. This may involve an interplay between two pacemaking c
urrents (L-type calcium channel current and hyperpolarization-activate
d current. Whether NO modulates the vagal control of HR recovery from
actual exercise remains to be determined.