[Chronic and acute effect of cycletanine in NO-dependent hypertensive pregnant rats].
Decreased response to vasopressor agents characterizes pregnancy. Endothelium-derived relaxing factors and vasodilating prostaglandins play an important role in the vascular tone during pregnancy. Since inhibition of nitric oxide (NO) biosynthesis induced by NO2-arginine enriched diet produced hypertension we measured in vivo cardiovascular responses to PGF2 alpha, L-arginine (L-arg) and cicletanine (Cic, IPSEN, France) which enhances PGI2 production. From day 13 to day 20 of gestation 4 groups of female Wistar rats were fed NO2-arg (31 mg/kg/d), NO2-arg+Cic (10 mg/kg/d), Cic enriched or control diet (C). Mean arterial pressure (MAP) was measured via a carotid catheter in anesthetized rats. Injection of PGF2 alpha (50 micrograms/kg) in jugular vein significantly increased MAP in the NO2-arg group versus, NO2-arg+Cic, Cic and C group (+23.5 +/- 3.3 vs +15.7 +/- 2.2, +15.8 +/- 2.2 and +17 +/- 1.85 mmHg; p < 0.01). Injection of L-arg (100 mg/kg) or Cic (1 mg/kg) 5 min before PGF2 alpha produced no modification in MAP in C and Cic group. Likewise in NO2-arg group injection of L-arg or Cic produced a diminished pressor response to PGF2 alpha (+23.5 +/- 3.3 vs -17.5 +/- 1.7 mmHg; p < 0.05 and +15.2 +/- 2.4 mmHg; p < 0.01 respectively). In NO2-arg+Cic group, only injection of Cic induced a diminished pressor response to PGF2 alpha which is more important without L-arg (+15.7 +/- 2.2 vs +9.1 +/- 1.3 mmHg; p < 0.001) or with L-arg (+13.6 +/- 1.5 vs +9.1 +/- 1.3 mmHg; p < 0.01). Cicletanine also significantly diminished the proteinuria in the NO2-arg+Cic group versus NO2-arg group (13.9 +/- 4.36 vs 63.4 +/- 21.6 mmHg; p < 0.01). IN CONCLUSION, chronic NO synthesis inhibition enhanced blood pressure and pressor responses to PGF2 alpha during pregnancy in rats. Chronic administration of cicletanine in Wistar pregnant rats decreases the response to vasopressor agents like PGF2 alpha. Moreover acute and chronic administration of cicletanine blunted the pressor effect, which was lower than in normal gestation.
Van Overloop
B
B
CNRS URA 60, Faculté de Pharmacie, Université Louis-Pasteur, Illkirch-Graffenstaden.
Pernot
F
F
Dité
C
C
Droy-Lefaix
M T
MT
Gairard
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019335:Nitroarginine; D010120:Oxytocics / Q000494:pharmacology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology; D011270:Pregnancy, Animal; D011460:Prostaglandins F / Q000494:pharmacology; D011507:Proteinuria; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D010120:Oxytocics; D011460:Prostaglandins F; D011725:Pyridines; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D015237:Dinoprost; C038068:cicletanine
Effet chronique et aigu du ciclétanine chez la rate gestante en hypertension NO-dépendante.