In our experimental study we found that the participation of BK(Ca2+) and K(ATP) potassium ion channels in the contractility of human term pregnant myometrium in labor is probably different.
Our data are consistent with previous studies of the enhanced efficiency of the beta(2)-adrenergic agonist, when administered together with the phosphodiesterase 4-inhibitor. Moreover we have shown that rolipram alone has a more profound effect on oxytocin-induced contractions than salbutamol alone.
The aim of the study was to evaluate the participation of ligand-sensitive potassium large conductance calcium-activated channels (BK Ca ) and ATP-sensitive potassium channels in uterine smooth muscle reactivity during different stages of the experimentally induced proliferatory and secretory phase in the sexual cycle in ovariectomised rabbits in vitro.The myometrial reactivity to oxytocin (10 -6 mol·l -1) was investigated by an in vitro method in female rabbits 14 days after ovariectomy treated with 17-estradiol -1 mg/kg/day i.m. for 7 days, or with a combination of progesterone 2 mg/kg/day s.c. for 7 days and 17-estradiol -0.2 mg/ kg/day (day 3-7). The strips of myometrial smooth muscle were incubated with a specific opener (NS 1619) and an antagonist (TEA) of potassium large conductance calcium-activated channel, or with a specific opener (pinacidil) and an antagonist (glybenclamide) of ATP-sensitive potassium channels before the administration of oxytocin.NS1619 produced more potent inhibition of the oxytocin-induced contraction during the gestagen dominance (experimental secretory phase) than the one observed during the oestrogen dominance (experimental proliferatory phase). TEA antagonized the NS1619 induced inhibition of the myometrial contraction.In the matter of K ATP potassium channels, after the administration of pinacidil we observed a similar situation in the changes of myometrial contractility. Pinacidil produced more pronounced inhibition of oxytocin-induced contraction during the secretory phase, and its effect was abolished by the selective inhibitor glybenclamide.Our experimental results indicate that both potassium large conductance calcium-activated channels and ATP-sensitive potassium channels significantly participate in the regulation of myometrial oxytocin-induced contractions and the activity of these channels is probably influenced by the levels of oestrogens and gestagens.
A b s t r a c tThe study discusses the problem of role of various substances in the mechanisms of contraction and relaxation of human term pregnant myometrium in the experimental in vitro conditions. Human myometrium tissue samples were collected from term pregnant women who had to undergo Caesarean section. The effects of potassium ion channels openers and closers, phosphodiesterase inhibitors and tachykinins were measured in the reactivity of human term pregnant myometrium in the experimental in vitro conditions. Specific agonist-opener of K ATP potassium ion channels -pinacidil significantly reduced contractile activity of human term pregnant myometrial strips induced by administration of oxytocin in in vitro conditions, while the effect of specific agonist-opener of BK Ca2+ potassium ion channels -NS1619 was not significant. Glibenclamide, specific K ATP potassium ion channels antagonist-closer significantly increased contractile activity of human term pregnant myometrial strips in in vitro conditions. The contractile effect of specific antagonist-closer of BK Ca2+ potassium ion channels -tetraethylammonium was not significant. Phosphodiesterase-4 inhibitor -rolipram and phosphodiesterase-5 inhibitor -sildenaphil led to statistically significant decrease of oxytocin-induced contractile activity in human term pregnant myometrial strips in in vitro conditions. Tachykinins -neurokinin A, neurokinin B and substance P markedly stimulated the activity of the human term pregnant myometrial strips in in vitro conditions.The results showed the different effectiveness of potassium ion channels openers and closers, phosphodiesterase inhibitors as well as tachykinins in the mechanisms of contraction and relaxation of human term pregnant myometrium in in vitro conditions.
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