Arrest of preterm labour and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor

Lees, C.; Campbell, Stuart; Jauniaux, Eric; Brown, Richard N; Ramsay, Bruce A.; Gibb, D. M. F.; Martin, John F.; Moncada, Salvador

doi:10.1016/s0140-6736(94)92468-6

Cited by 207 publications

(83 citation statements)

References 8 publications

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“…In 1994, Lees et al (11) reported that transdermal nitroglycerin patches suppressed uterine contractions in all 20 episodes of preterm labor that occurred in 13 consecutive women enrolled in a pilot study, and they hence suggested that this nitric oxide donor could be an effective and safe tocolytic agent.…”

Section: Discussionmentioning

confidence: 99%

Transdermal Nitroglycerin Versus Oral Nifedipine for Suppression of Preterm Labor

et al. 2015

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Background: One of the most serious complications of pregnancy is preterm labor (PTL) and delivery. Further, there are different tocolytic agents available to enhance the time of delivery. Objectives: The aim of this study was to compare the effectiveness of transdermal nitroglycerin (glyceryl trinitrate, GTN) and oral nifedipine for managing preterm labor. Patients and Methods:This was a randomized clinical trial involving women who were admitted to our hospital with a diagnosis of PTL. Group one received transdermal GTN, whereas group two received oral nifedipine. All vital signs, fetal heart rate (FHR), contractions, dilation, and effacement, as well as gestation age at the time of delivery, have been monitored and evaluated in both groups of patients. Our main goal was the postponement of delivery so as to secure the most beneficial effect of primary corticosteroid administration for the fetus. Results: Both groups were matched regarding age, gestational age at the time of tocolytic therapy, height of fundus, history of pregnancy, abortion, delivery, and stillbirth, primary body temperature, and systolic and diastolic blood pressure. Those who received GTN had a more prolonged delay of delivery. Also, the GTN group had infants with better one-and five-minute Apgar scores. Although both groups reported minimal side effects, tachycardia and nausea were reported more frequently in GTN patients. Conclusions: Transdermal GTN was shown to be more effective in controlling PTL compared to oral nifedipine in terms of both maternal and neonatal effects.

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Section: Discussionmentioning

confidence: 99%

Transdermal Nitroglycerin Versus Oral Nifedipine for Suppression of Preterm Labor

et al. 2015

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“…For example, nitrosoglutathione appears to show platelet selective effects when administered in vivo whereas the classical organic nitrates have little or no effect on platelets at therapeutic doses [49]. The clinical indications of such compounds may then be much broader than angina and could include prevention of the re-occlusion of coronary afteries after angioplasty [50] and arresting premature labour [51]. Interestingly NO" itself is being used in the treatment of pulmonary hypertension [52].…”

Section: Nitric" Oxide Donorsmentioning

confidence: 99%

Nitric oxide and oxygen radicals: a question of balance

1995

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The production of superoxide and nitric oxide individually has been associated with the development of several diseases but only recently has it been realised that interactions between them may also be important in disease pathology. The central hypothesis which is emerging is that the balance between nitric oxide and superoxide generation is a critical determinant in the aetiology of many human diseases including atherosclerosis, neurodegenerative disease, ischaemia-reperfusion and cancer. These ideas are discussed in this short overview and placed in the context of the current and future status of therapies which could modulate the balance between nitric oxide and superoxide.

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“…[1][2][3] Drugs used to treat preterm labor, such as prostaglandin synthesis inhibitors, calcium channel antagonists and ␤-adrenoceptor agonists, have only short-lived effects or have potential side effects for mother and fetus. 4,5 Agents that have been used more recently, such as oxytocin receptor antagonists 6 and nitric oxide (NO) donors, 7 are currently the focus of intensive research, but early reports suggest that they will not confer major benefits. One reason there is no effective method of treating preterm labor is our limited knowledge of the mechanisms that control myometrial quiescence during pregnancy and its contractile state in normal and preterm labor.…”

mentioning

confidence: 99%

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

Barber¹,

Robson

Lyall³

1999

The American Journal of Pathology

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The nitric oxide (NO)-cGMP pathway has been proposed as a mechanism for relaxation of myometrium during pregnancy and as a modulator of labor. Carbon monoxide (CO) , produced by hemeoxygenases (HO-1 and HO-2) , also activates soluble guanylate cyclase to increase cGMP. A recent study reported a large increase in HO-1 and HO-2 proteins during pregnancy , suggesting that the HO-CO pathway may be important in the maintenance of uterine quiescence during pregnancy. In this study we used Western blotting , reverse transcription-polymerase chain reaction , and immunohistochemistry to determine HO-1 and HO-2 expression in nonpregnant , pregnant, and laboring myometrium. Immunolocalization of HO was also compared with endothelial and inducible nitric oxide synthases (eNOS and iNOS). In contrast to HO-1 protein , which was not detected in myometrium , HO-2 protein and mRNA were constitutively expressed , although there were no differences in expression between the groups. eNOS was expressed in endothelial cells but not in myometrial smooth muscle. iNOS protein was not detected in myometrium. These data do not support an up-regulation of HO-1 and HO-2 during pregnancy and are not consistent with a role for NO or a major role for CO in human myometrial quiescence. Our results are also in keeping with HO-2 being an noninducible protein. Although spontaneous preterm birth (delivery before 37 weeks) accounts for 5 to 10% of all births, it is associated with up to 70% of neonatal deaths. It is also responsible for up to 75% of neonatal morbidity with considerable long-term morbidity in the child. 1-3 Drugs used to treat preterm labor, such as prostaglandin synthesis inhibitors, calcium channel antagonists and ␤-adrenoceptor agonists, have only short-lived effects or have potential side effects for mother and fetus. 4,5 Agents that have been used more recently, such as oxytocin receptor antagonists 6 and nitric oxide (NO) donors, 7 are currently the focus of intensive research, but early reports suggest that they will not confer major benefits. One reason there is no effective method of treating preterm labor is our limited knowledge of the mechanisms that control myometrial quiescence during pregnancy and its contractile state in normal and preterm labor. 8,9 NO, produced by the enzyme nitric oxide synthase (NOS), binds to the heme prosthetic moiety of the soluble guanylate cyclase, leading to increased cGMP production and smooth muscle relaxation. Carbon monoxide (CO) also binds to heme and activates soluble guanylate cyclase. 10 Discrepancies in localization of NOS and guanylate cyclase in the brain indicate that a substantial portion of guanylate cyclase may not serve as a target for NO. 11 CO is produced by heme oxygenase (HO), a microsomal enzyme that oxidatively cleaves heme, a prooxidant, to produce biliverdin and CO in the presence of NADPH-cytochrome P 450 reductase and NADPH. 12 HO consists of two homologous isoenzymes: HO-1, which is inducible, and HO-2, which is constitutive. 13,14 HO-1 is expressed at high concent...

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Arrest of preterm labour and prolongation of gestation with glyceryl trinitrate, a nitric oxide donor

Cited by 207 publications

References 8 publications

Transdermal Nitroglycerin Versus Oral Nifedipine for Suppression of Preterm Labor

Transdermal Nitroglycerin Versus Oral Nifedipine for Suppression of Preterm Labor

Nitric oxide and oxygen radicals: a question of balance

Hemoxygenase and Nitric Oxide Synthase Do Not Maintain Human Uterine Quiescence during Pregnancy

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