The Effect of Potassium Channel Opener Pinacidil on the Non‐Pregnant Rat Uterus

Novaković, R; Milovanović, Srđan; Protić, Dragana; Djokić, Jelena; Heinle, H.; Gojkovic-Bukarica, Ljiljana

doi:10.1111/j.1742-7843.2007.00096.x

Cited by 16 publications

(20 citation statements)

References 32 publications

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“…, 2008). Various agents, including levcromakalim, pinacidil and nicorandil, that act by opening K + channels, have been used for the treatment of dysfunctional smooth muscle activity (Novakovic et al. , 2007).…”

Section: Introductionmentioning

confidence: 99%

Hydrogen peroxide affects contractile activity and anti‐oxidant enzymes in rat uterus

Appiah

Milovanović

Radojičić

et al. 2009

British J Pharmacology

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Background and purpose:The effects of hydrogen peroxide (H2O2) on uterine smooth muscle are not well studied. We have investigated the effect and the mechanism of action of exogenous hydrogen peroxide on rat uteri contractile activity [spontaneous and calcium ion (Ca 2+ )-induced] and the effect of such treatment on anti-oxidative enzyme activities. Experimental approach: Uteri were isolated from virgin Wistar rats and suspended in an organ bath. Uteri were allowed to contract spontaneously or in the presence of Ca 2+ (6 mM) and treated with H2O2 (2 mM-3 mM) over 2 h. Anti-oxidative enzyme activities (manganese superoxide dismutase-MnSOD, copper-zinc superoxide dismutase-CuZnSOD, catalase-CAT, glutathione peroxidase-GSHPx and glutathione reductase-GR) in H2O2-treated uteri were compared with those in uteri immediately frozen after isolation or undergoing spontaneous or Ca 2+ -induced contractions, without treatment with H2O2. The effect of inhibitors (propranolol, methylene blue, L-NAME, tetraethylamonium, glibenclamide and 4-aminopyridine) on H2O2-mediated relaxation was explored. Key results: H2O2 caused concentration-dependent relaxation of both spontaneous and Ca 2+ -induced uterine contractions. After H2O2 treatment, GSHPx and MnSOD activities were increased, while CuZnSOD and GR (In Ca 2+ -induced rat uteri) were decreased. N w -nitro-L-arginine methyl ester antagonized the effect of H2O2 on Ca 2+ -induced contractions. H2O2-induced relaxation was not affected by propranolol, potentiated by methylene blue and antagonized by tetraethylamonium, 4-aminopyridine and glibenclamide, with the last compound being the least effective. Conclusions and implications: H2O2 induced dose-dependent relaxation of isolated rat uteri mainly via changes in voltagedependent potassium channels. Decreasing generation of reactive oxygen species by stimulation of anti-oxidative pathways may lead to new approaches to the management of dysfunctional uteri.

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Section: Introductionmentioning

confidence: 99%

Hydrogen peroxide affects contractile activity and anti‐oxidant enzymes in rat uterus

Appiah

Milovanović

Radojičić

et al. 2009

British J Pharmacology

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“…There are differences between experimental studies in animals (16,17,18) and clinical studies in humans (19,20). There are differences between experimental studies in animals (16,17,18) and clinical studies in humans (19,20).…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Contraction and Relaxation in Human Term Pregnant Myometrium

Sadlonova

Dokus

Janicek³

et al. 2012

Acta Medica Martiniana

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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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“…Pinacidil is an antihypertensive agent, which can relax various smooth muscles (Davies et al, 1996;Gojkovic and Kazic, 1999;Gojkovic-Bukarica et al, 2010), including the animal (Piper et al, 1990;Mandi et al, 2005;Novakovic et al, 2007) and human uterus (Morrison et al, 1993, Khan et al, 1998. The mechanism of action has not yet been fully established, but has been named that relaxation responses are associated with the opening of K + channels and characterized by its ability to cause cell hyperpolarization by primarily increasing potassium ion permeability (Bray et al, 1987).…”

Section: Introductionmentioning

confidence: 99%

Potassium channels opener pinacidil have multiple effects on KCl-elicited contractions of isolated non-pregnant rat uterus

Novaković¹,

Milovanović²,

Ćupić³

et al. 2011

Acta vet. (Beogr.)

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The effects of K+ channel opener, pinacidil on contractions provoked by contraction-stimulating KCl were investigated on isolated uterus of non-pregnant rats in oestrus. Pinacidil produced a more potent inhibition of 20 mM KCl-elicited contractions (pD2 = 6.57 μM) than of 40 or 80mMKCl-elicited contractions (pD2=5.11 and 5.19 μM, respectively). Glibenclamide, a selective blocker of adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, antagonized the pinacidil-induced inhibition of contractions elicited by 20 mM KCl in a competitive manner. However, the pinacidil-induced inhibition of contractions provoked by 40 and 80 mM KCl glibenclamide was unable to prevent them. Pinacidil ability to completely relax the non-pregnant uterus pre-contracted with K+-rich solution suggests that K+ channelindependent mechanism(s) also plays a part in its relaxant effect

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The Effect of Potassium Channel Opener Pinacidil on the Non‐Pregnant Rat Uterus

Cited by 16 publications

References 32 publications

Hydrogen peroxide affects contractile activity and anti‐oxidant enzymes in rat uterus

Hydrogen peroxide affects contractile activity and anti‐oxidant enzymes in rat uterus

Mechanisms of Contraction and Relaxation in Human Term Pregnant Myometrium

Potassium channels opener pinacidil have multiple effects on KCl-elicited contractions of isolated non-pregnant rat uterus

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