CICLETANINE AND VASOPRESSOR RESPONSE TO P GP(2)ALPHA IN NO-DEPENDENT HYPERTENSIVE PREGNANT RATS

Decreased response to vasopressor agents characterizes pregnancy. Endo thelium-derived relaxing factors and vasodilating prostaglandins play an important role in the vascular tone during pregnancy. Since inhibit ion of nitric oxide (NO) biosynthesis induced by NO2-arginine enriched diet produced hypertension we measured in vivo cardiovascular respons es to PGF(2) alpha, L-arginine (L-arg) and cicletanine (Cic, IPSEN, Fr ance) which enhances PGI(2) production. From day 13 to day 20 of gesta tion 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 arteri al pressure (MAP) was measured via a carotid catheter in anesthetized rats. Injection of PGF(2) alpha(50 mu g/kg,) in jugular vein significa ntly 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 befo re PGF(2) alpha produced no modification in MAP in C and Cic group. Li kewise in NO2-arg group injection of L-arg or Cic produced a diminishe d presser response to PGF(2) alpha (+23,5+/-3,3 vs-17,5+/-1,7 mmHg :p < 0,05 and vs +15,2+/-2,3 mmHg; p < 0,01 respectively). In NO2-arg+Cic group, only injection of Cic induced a dimished presser response to P GF(2) 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 PGF(2) alpha during p regnancy in rats. Chronic administration of cicletanine in Wistar preg nant rats decreases the response to vasopressor agents like PGF(2) alp ha. Moreover acute and chronic administration of cicletanine blunted t he presser effect, which was lower than in normal gestation.