The purpose of this study was to establish whether endogenous L-arginine/nitric oxide(L-ARG/NO) pathway system exists in human uterine smooth muscle and this muscle is responsive to exogenous nitric oxide(NO). the difference of the effect of NO
on
myometrial contractility between pregnant and non-pregnant uterus were also observed.
Isometric tension of human myometrial strips from pregnant(n=10) and non-pregnant(n=20) women were measured in vitro in response to L-arginine(L-ARG), N-nitro-L-arginine methyl(L-NAME), or Nw-nitro-L-arginene(L-NNA) that modulate endogenous
L-ARG/NO
action as well as to exogenous NO that is generated by photolysis of NO-carrying compound such as streptozotocin(STZ). Changes of amplitude and cycle length of phasic contraction by photolysis of STZ with various concentration were measured and
compared
between pregnant and non-pregnant uterus. Cyclic guanosine monophosphate(cGMP) levels were measured by radioimmunoassay in various testing conditions of myometrial tissues.
Spontaneously contracting non-pregnant myometrial strips were relaxed by application of L-ARG(10-3mol/L). This L-ARG-induced relaxation was obliterated by application of L-NAME(10-3mol/L). These L-ARG-or L-NAME-induced effects were exagerated in
the
lipopolysaccharide(10μg/ml)-pretreated or pregnant myometrium. The non-pregnant myometrial contractile activity was decreased by exogenous NO dose-dependently, that is, by photolysis of the STZ with the concentration of 10-6, 10-5, 10-4, and
10-3
mol/L, the mean percent decrease of amplitude were 8.3±3.2%, 15.8±6.1%, 26.4±9.3%, and 45.7±18.6%, respectively and the mean percent delay of cycle length were 14.3±6.4%, 24.5±9.5%, 48.8%±15.5%, and 120.6±51.5%, respectively. These mean
percent
changes of amplitude and cycle length under the same dose of STZ(10-4 mol/L) were greater in pregnant myometriums compared with non-pregnant ones(26.4±9.3% vs 50.5±14.1%, 48.8±15.5% vs 73.3±30.0%, mean±SD, p<0.01, respectively) suggesting
that
the
pregnant uterus is more sensitive to NO than nonpregnant one. Cyclic GMP levels in the myometrial tissue were increased by exogenous NO dose-dependently, that is, by photolysis of STZ with the concentration of 10-4 mol/L, the cGMP levels were
4.82±1.52, 5.96±1.67, and 8.97±1.91 fmol/mg tissue according to the UV light exposure time of 1, 2, and 4 minutes, respectively, But in methylene blue pretreated myometrium, the cGMP level as lower than that of control even at 4 minutes of
exposure
time.
These findings suggest that endogenous L-ARG/NO pathway system exists in human uterine smooth muscle and NO is regarded as, at least in part, regulator of human myometrial relaxation or quiescence during pregnancy by modulating cGMP levels.
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