ENDOTHELIN-1 IS HYPOTENSIVE IN A RAT MODEL OF PREECLAMPSIA

Hypertensive pregnant rats with inhibition of NO synthase are frequent ly considered as model of pre-eclampsia with proteinuria, hypertension and elevated endothelin (ET-1) blood levels. We describe here the car diovascular in vivo effects of ET-1 in this rat model since ET-1 and N O are both important vasoactive mediators in uteroplacental circulatio n. From day 13 of gestation 2 groups of Wistar female rats were fed co ntrol (C) or nitroarginine enriched diet (0,063 %, Treated : T). On ge stational day 20 mean arterial pressure (MAP, mmHg) was measured via a carotid catheter in pentobarbital (60 mg/kg) anesthetized rats. After chronic NO synthase inhibition hypertension develops; MAP on day 20 : 158 +/- 2.2 in T and 113 +/- 2.2 in C, p < 0,001. ET-1 bolus injectio n (0.1 nmol/kg) is rapidly followed by a decrease in blood pressure si gnificantly more important in T : 46 +/- 5.1 than in C: -30 +/- 2.2. I n vivo depressor effect is blocked by the specific antagonist BQ-788. After inhibition of cycloxygenase with acetylsalicylic acid (27 mu mol /kg, 30 min before) the hypotension is not modified. Since NO and PGI( 2) productions are not expected in our conditions, vasodepressor effec t can be explained by an endothelial hyperpolarazing factor (EDHF). In conclusion in vivo ET-1 hypotensive effects in pregnant rats are medi ated by ETB receptors and more pronounced in hypertensive NO-deprived animals.