Gl. Raymond et al., FORCE AND INTRACELLULAR CA2-MEDIATED RELAXATION OF RAT ANOCOCCYGEUS MUSCLE AND THE EFFECTS OF CYCLOPIAZONIC ACID( DURING NANC), Clinical and experimental pharmacology and physiology, 22(10), 1995, pp. 717-723
1. Simultaneous recordings of tension and [Ca2+](i) during NANC-mediat
ed relaxation were made in the rat anococcygeus muscle under various c
onditions. 2. In muscles precontracted with guanethidine, nitrergic st
imulations at 2 Hz produced a rapid decrease in both the tension and [
Ca2+](i). 3. The nitric oxide synthase inhibitor, N-G-nitro-L-Arginine
(NOLA, 100 mu mol/L) completely abolished the decreases in the [Ca2+]
(i) and force response of the NANC-mediated relaxation, 4. Noradrenerg
ic-mediated contractions elicited by electrical field stimulation were
potentiated by the addition of NOLA. In the absence of NOLA, the moto
r responses were larger in magnitude at 10 Hz stimulation than at 2 Hz
. After NOLA, both the force response and the associated rise in [Ca2](i) were substantially increased in comparison to the control stimula
tions. Proportionately the potentiation of the 2 Hz response was of a
far greater magnitude than that of the 10 Hz response. 5. The guanylat
e cyclase inhibitor methylene blue (10 mu mol/L), partially inhibited
the force and [Ca2+](i) response of the NANC relaxation. 6. Following
exposure of the muscles to the sarcoplasmic reticulum Ca2+-ATPase inhi
bitor, cyclopiazonic acid, (10 mu mol/L) the responses to NANC stimula
tion were inhibited. The attenuated relaxation response displayed a bi
-phasic timecourse and the Ca2+ change in comparison to that of the co
ntrol was markedly smaller. In some cases, a relaxation was observed w
ith no detectable change in the [Ca2+](i). 7. The results suggest that
part of the relaxation response observed with NANC-mediated relaxatio
n in the rat anococcygeus is dependent on Ca2+ sequestration into the
sarcoplasmic reticulum. However, other Ca2+ lowering mechanisms and po
ssible Ca2+ independent mechanisms may also contribute to the NANC rel
egation response.