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.