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Lack of beneficial effects of the NO‐donor, molsidomine, in the L‐NAME‐induced pre‐eclamptic syndrome in pregnant rats
Author(s) -
Richer Christine,
Boulanger Henri,
EsSlami Samira,
Giudicelli JeanFrançois
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16084.x
Subject(s) - molsidomine , blood pressure , endocrinology , medicine , angiotensin ii , chemistry , nitric oxide
1 In pregnant rats, chronic NO‐synthase inhibition induces the development of a pre‐eclamptic syndrome, characterized by an increase in maternal blood pressure, a loss of vascular refractoriness to pressor stimuli, a reduction in litter size and a decrease in pups (and maternal) weight. We investigated whether a NO‐donor, molsidomine, administered during NO synthase inhibition, could restore a normal pregnancy. 2 Pregnant rats were given daily, starting from day 14 of gestation, saline (controls), or L‐NAME (50 mg kg −1 d −1 ), or molsidomine (15 or 30 mg kg −1 d −1 ), or the L‐NAME + molsidomine combinations. Maternal blood pressure and body weight, litter size, pups weight and vascular reactivity to pressor stimuli (angiotensin II, noradrenaline, electrical stimulation of the spinal cord) were investigated. 3 L‐NAME alone, as compared to controls, increased maternal blood pressure, reduced litter size (−59%), increased foetal reabsorptions (+625%) and decreased foetal weight (−10%). Vascular reactivity to pressor stimuli was enhanced. 4 Molsidomine alone, as compared to controls, dose‐dependently decreased maternal blood pressure but had no effect on vascular reactivity and, whatever the dose, on foetal outcome. 5 The L‐NAME‐molsidomine combinations dose (of molsidomine)‐dependently limited the rise in maternal blood pressure induced by L‐NAME alone but unexpectedly, dose‐dependently and significantly worsened pregnancy evolution, e.g., at 30 mg kg −1 d −1 : litter size (−80%), foetal reabsorptions (+1025%), foetal weight (−24%). Vascular reactivity to pressor stimuli was paradoxically further enhanced. 6 Thus, in a chronic NO deprivation‐induced model of pre‐eclampsia in rats, molsidomine, possibly because of its hypotensive action, worsens the foetal outcome, which questions the usefulness of NO‐donors in pre‐eclamptic women.