title: Effect of i1 imidazoline receptor agonist, moxonidine, in nitric oxide-deficient hypertension in pregnant rats.
abstract: Decreased nitric oxide production has been reported in preeclampsia, which is also frequently associated with glucose intolerance. It was thus considered of interest to investigate the effects of moxonidine, a centrally acting antihypertensive drug that reduces insulin resistance, in a rat model of preeclampsia. Hypertension was induced in Wistar rats by dietary l-NNA (N(omega)-nitro-L-arginine, 0.063%, 31 mg/kg/d, days 13-19 of gestation) and, over the same period, moxonidine or vehicle was administered orally (2 mg/kg/d by gavage). On day 20, blood pressure was measured in the pentobarbital anesthetized animals, glucose tolerance was tested (2 g/kg glucose i.p.), and morphologic studies were conducted on the litter to determine the benefits with respect to fetal outcome. Hypertension was reduced with daily moxonidine treatment (P < 0.05). Basal plasma insulin and insulin/glucose index were decreased with moxonidine treatment evidencing improved insulin sensitivity in the control and l-NNA-treated pregnant rats (P < 0.05). After glucose challenge, plasma insulin increased in all the groups as expected and plasma insulin and insulin/glucose index were significantly higher in the l-NNA group than in the control, moxonidine, or l-NNA + moxonidine groups (P < 0.05 for time 60 minutes). Thus, moxonidine improved glucose tolerance in l-NNA-treated pregnant rats. Moreover, moxonidine treatment very effectively decreased the number of necroses (1 necrosis in 71 fetuses in the l-NNA + moxonidine group versus 15 necroses in 79 fetuses in the l-NNA group, P < 0.01). In conclusion, the 7-day treatment with moxonidine suppressed hypertension and reduced glucose intolerance and fetal necrosis, thus demonstrating the effectiveness of moxonidine in the preeclamptic model.
authors.affiliation: Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Faculté de Pharmacie, Illkirch, France. gairard@aspirine.u-strasbg.fr
authors.forename: Alexis
authors.initials: A
authors.lastname: Gairard
authors.forename: Visitacion
authors.initials: V
authors.lastname: Lopez-Miranda
authors.forename: Fanny
authors.initials: F
authors.lastname: Pernot
authors.forename: Jean F
authors.initials: JF
authors.lastname: Beck
authors.forename: Geneviève
authors.initials: G
authors.lastname: Coumaros
authors.forename: Bruno
authors.initials: B
authors.lastname: Van Overloop
authors.forename: Benoît
authors.initials: B
authors.lastname: La Roche
authors.forename: Christian
authors.initials: C
authors.lastname: Koehl
authors.forename: Marie O
authors.initials: MO
authors.lastname: Christen
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000473:pathology; D005951:Glucose Tolerance Test; D046110:Hypertension, Pregnancy-Induced / Q000188:drug therapy* / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D009336:Necrosis; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000819:agonists*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007093:Imidazoles; D054755:Imidazoline Receptors; D011955:Receptors, Drug; D009569:Nitric Oxide; C043482:moxonidine; D019001:Nitric Oxide Synthase