HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effect of methyldopa on renal function in rats with L-NAME-induced hypertension in pregnancy.

AbstractBACKGROUND:
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.
AuthorsE Podjarny, S Benchetrit, B Katz, J Green, J Bernheim
JournalNephron (Nephron) Vol. 88 Issue 4 Pg. 354-9 (Aug 2001) ISSN: 1660-8151 [Print] Switzerland
PMID11474231 (Publication Type: Comparative Study, Journal Article)
CopyrightCopyright 2001 S. Karger AG, Basel.
Chemical References
  • Nitrates
  • Methyldopa
  • Arginine
  • Diltiazem
  • NG-Nitroarginine Methyl Ester
Topics
  • Animals
  • Arginine (therapeutic use)
  • Diltiazem (therapeutic use)
  • Drinking
  • Eating
  • Female
  • Hypertension (chemically induced, complications, drug therapy)
  • Kidney (drug effects, physiopathology)
  • Methyldopa (therapeutic use)
  • NG-Nitroarginine Methyl Ester
  • Nitrates (urine)
  • Pregnancy
  • Pregnancy Complications (drug therapy, urine)
  • Rats
  • Rats, Wistar

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: