Modification of the effect of nifedipine in the pregnant rat myometrium: The influence of progesterone and terbutaline

Hajagos-Tóth, Judit; Falkay, George; Gáspár, Róbert

doi:10.1016/j.lfs.2009.08.008

Cited by 22 publications

(27 citation statements)

References 17 publications

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“…[22] established that a P4-mediated mechanism favours the expression of the long form, in the presence of which the channel displays lower activity. We earlier observed [21] that in vivo P4 pre-treatment (for 7 days) decreased the maximum inhibitory effect of nifedipine and increased its EC 50 in vitro , and also abolished the ability of nifedipine to delay labour in hormone-induced pre-term delivery in rats in vivo [31]. These results correlate with the hypothesis that P4 decreases the activity of the L-type Ca 2+ channels.…”

Section: The Mechanism Of Action Of Ccbs On the Pregnant Myometriumsupporting

confidence: 72%

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Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Gáspár

Hajagos-Tóth

2013

Pharmaceuticals

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Dihydropyridine Ca2+ channel blockers (CCBs) are widely accepted in the treatment of premature labour. Their mechanism of action in tocolysis involves the blockade of L-type Ca2+ channels, influenced by the Ca2+-activated K+ channels, beta-adrenergic receptors (β-ARs) and sexual hormones. In clinical practice, most experience has been gained with the use of nifedipine, whose efficacy is superior or comparable to those of β-agonists and oxytocin antagonists. Additionally, it has a favourable adverse effect profile as compared with the majority of other tocolytics. The most frequent and well-tolerated side-effects of CCBs are tachycardia, headache and hypotension. In tocolytic therapy efforts are currently being made to find combinations of tocolytic agents that yield better therapeutic action. The available human and animal studies suggest that the combination of CCBs with β-AR agonists is beneficial, although such combinations can pose risk of pulmonary oedema in multiple pregnancies and maternal cardiovascular diseases. Preclinical data indicate the potential benefit of combinations of CCBs and oxytocin antagonists. However, the combinations of CCBs with progesterone or cyclooxygenase inhibitors may decrease their efficacy. The CCBs are likely to remain one of the most important groups of drugs for the rapid inhibition of premature uterine contractions. Their significance may be magnified by further clinical studies on their combined use for tocolysis.

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Section: The Mechanism Of Action Of Ccbs On the Pregnant Myometriumsupporting

confidence: 72%

“…The resultant effect of the increase in cAMP level and the activation of Ca v 1.2 channels cause a weaker smooth muscle relaxation. In the opposite case, when nifedipine is administered first, the Ca v 1.2 channels are blocked, hence terbutaline cannot activate them [21]. …”

Section: The Mechanism Of Action Of Ccbs On the Pregnant Myometriummentioning

confidence: 99%

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Gáspár

Hajagos-Tóth

2013

Pharmaceuticals

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“…The relaxing effect of FPCA was less significant than that of salbutamol. Unlike FPCA, the relaxing effect of salbutamol on myometrium is mediated by the large‐conductance voltage‐ and Ca 2+ ‐activated K + channel (BK Ca )‐induced inactivation of L‐type VGCC, suggesting a more important role for L‐type VGCC compared with CRAC channels in the amplitude of myometrial contractions.…”

Section: Discussionmentioning

confidence: 99%

Orai1 protein expression and the role of calcium release‐activated calcium channels in the contraction of human term‐pregnant and non‐pregnant myometrium

Šutovská¹,

Kočmálová²,

Sadlonova³

et al. 2014

J of Obstet and Gynaecol

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“…Every alteration in the myometrial contractility has an impact on the function of calcium channels and calcium influx into the myometrial cells. Sexual hormones can alter the isoforms of voltage-dependent L-type calcium channels, which may influence contractility and pharmacological reactivity (27). Calcium channel blockers inhibit calcium re-uptake via these channels and induce smooth muscle relaxation.…”

Section: Physiological Factors and Therapeutic Targets Of Pregnant Utmentioning

confidence: 99%

Obesity in pregnancy: a novel concept on the roles of adipokines in uterine contractility

et al. 2017

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Obesity is a global health problem even among pregnant women. Obesity alters quality of labor, such as preterm labor, prolonged labor, and higher oxytocin requirements in pregnant women. The most important factors to play a role in the altered gestational period and serve as drug targets to treat the consequences are female sexual hormones, calcium channels, adrenergic system, oxytocin, and prostaglandins. However, we have limited information about the impact of obesity on the pregnant uterine contractility and gestation time. Adipose tissue, which is the largest endocrine and paracrine organ, especially in obesity, is responsible for the production of adipokines and various cytokines and chemokines, and there are no reliable data available describing the relation between body mass index, glucose intolerance, and adipokines during pregnancy. Recent data suggest that the dysregulation of leptin, adiponectin, and kisspeptin during pregnancy contributes to gestational diabetes mellitus and pre-eclampsia. A preclinical method for obese pregnancy should be developed to clarify the action of adipokines and assess their impact in obesity. The deeper understanding of the adipokines-induced processes in obese pregnancy may be a step closer to the prevention and therapy of preterm delivery or prolonged pregnancy. Gestational weight gain is one of the factors that could influence the prenatal development, birth weight, and adiposity of newborn.

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Modification of the effect of nifedipine in the pregnant rat myometrium: The influence of progesterone and terbutaline

Abstract: It is concluded that the uterus-relaxing effect of nifedipine is weakened by progesterone and may be enhanced by low concentrations of beta-mimetics. However, the administration of terbutaline cannot precede the administration of nifedipine.

Cited by 22 publications

References 17 publications

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations

Orai1 protein expression and the role of calcium release‐activated calcium channels in the contraction of human term‐pregnant and non‐pregnant myometrium

Obesity in pregnancy: a novel concept on the roles of adipokines in uterine contractility

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