Cl. Murrant et al., THE EFFECT OF NITRIC-OXIDE AND ENDOTHELIN ON SKELETAL-MUSCLE CONTRACTILITY CHANGES WHEN STIMULATION IS ALTERED, Canadian journal of physiology and pharmacology, 75(5), 1997, pp. 414-422
To investigate the effect of endothelial-derived products on the force
of contraction of blood-perfused skeletal muscle, we infused S-nitros
o-N-acetylpenicillamine (SNAP, 10(-4) M) (a nitric oxide (NO) donor),
endothelin-1 (ET-1, 10(-8) M), N-acetylpenicillamine (NAP, 10(-4) M),
or Saline at a constant vascular concentration into the vascular bed o
f pump-perfused dog gastrocnemius-plantaris muscles in situ (n = 17).
Muscles performed isometric twitch contractions at 0.5, 1.5, and 4 Hz
and isometric tetanic contractions (150 ms, 50 Hz) at 12 and 40 contra
ctions/min. We perfused the muscle at a constant pressure at rest and
for the first 3 min of the 6-min contraction period, and then switched
to constant flow perfusion and infused the substance over the remaini
ng 3 min. Neither NAP nor saline had a significant effect on force of
contraction or perfusion pressure. SNAP significantly attenuated devel
oped force as compared with NAP at 40 contractions/min and at 1.5 and
4 Hz. The effect of SNAP on developed force was greater during twitch
than tetanic contractions. ET-l had no significant effect on twitch or
tetanic developed force. To test for these results on another mammali
an skeletal muscle preparation, we stimulated curarized trimmed mouse
soleus in vitro for 500 ms at 50 Hz at either 2 or 3 contractions/min
in the presence of SNAP (10(-4) M) or ET-1 (10(-9) M). SNAP, which inc
reased force at 1 contraction/90 s, had Ilo significant effect at the
higher contraction frequencies. The inhibition by ET-1 at 2 contractio
ns/min disappeared at 4 contractions/min. Therefore the effect of both
NO and ET-1 on mammalian skeletal muscle appears to be dependent upon
contraction pattern and frequency.