Key result
Methyldopa treatment normalized systolic blood pressure, improved creatinine clearance and proteinuria, and increased urinary nitrate excretion in rats with L-NAME-induced hypertension in pregnancy.
Why the study?
Does methyldopa improve renal function and nitric oxide synthesis in pregnant rats with L-NAME-induced hypertension?
Does methyldopa improve renal function and nitric oxide synthesis in pregnant rats with L-NAME-induced hypertension?
Methyldopa improves renal function and normalizes blood pressure in a rat model of pregnancy-induced hypertension, potentially via stimulating nitric oxide synthesis.
Hypothesis-generating in L-NAME rat preeclampsia model; leaves open human translation and should not change practice.
BACKGROUND: Pregnancy-induced hypertension is characterized by an increased sympathetic activity and probably by a decreased synthesis/activity of nitric oxide. The aim of the present study is to evaluate whether the beneficial action of the sympathetic antagonist methyldopa (a first-choice hypotensive agent in the treatment of PIH) may be associated to changes in nitric-oxide synthesis. METHODS: Forty pregnant Wistar rats received L-NAME (NO synthase inhibitor, 9-10 mg/kg/day) from mid-pregnancy (day 11) through to term. Some rats were treated with daltroban (TxA receptor antagonist, 60 mg/kg/day), diltiazem (calcium channel blocker, 30 mg/kg/day), methyldopa (central adrenergic antagonist, 400 mg/kg/day) or L-arginine (260 mg/kg/day) from mid-pregnancy. The effect of the different treatments on systolic blood pressure (SBP), creatinine clearance (CCR), urine protein excretion (UP) and urinary nitrate excretion (UNO(3), representing urine NO metabolite) were evaluated and the results compared with those found in normal pregnancy. Normal pregnant rats receiving similar treatment were used as controls. RESULTS: In normal pregnant (P) rats, SBP values decreased from 94 +/- 2 to 83 +/- 3 mm Hg at the end of pregnancy (p < 0.01) and CCR augmented significantly. Drug treatment had no significant effect. In NAME-treated rats, at the same period, the SBP augmented from 92 +/- 1 to 129 +/- 1.8 mm Hg (p < 0.01). At the end of pregnancy, NAME rats had significantly lower CCR values and higher UP excretion when compared with P rats. UNO(3) increased significantly in P and in P rats treated with methyldopa. As expected, in NAME rats UNO(3) excretion was significantly reduced. Treatment with methyldopa normalized SBP, improved CCR and proteinuria and was associated with an increase in UNO(3). Similar results were obtained with L-arginine treatment. Diltiazem lowered SBP significantly but had no effect on renal function or UNO(3) and daltroban had no effect. CONCLUSION: The increased UNO(3) found in NAME rats treated with methyldopa suggests that the vasoconstriction secondary to chronic NO inhibition may be partially related to an increased sympathetic activity. The efficient action of the sympathetic antagonist methyldopa may be due not only to its antihypertensive effects but also by its stimulating effect on NO synthesis leading also to an improvement of renal function.
No takes yet. Share an insight, caveat, or question.
Podjarny et al. (2001) studied L-NAME-Induced Hypertension in Pregnancy (n=40). Methyldopa vs. Normal pregnant rats and untreated L-NAME rats was evaluated on Systolic blood pressure, creatinine clearance, urine protein excretion, and urinary nitrate excretion. Methyldopa treatment normalized systolic blood pressure, improved creatinine clearance and proteinuria, and increased urinary nitrate excretion in rats with L-NAME-induced hypertension in pregnancy.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: