[Hypotensive effect of endothelin-1 in a rat model of pre-eclampsia].
Hypertensive pregnant rats with inhibition of NO synthase are frequently considered as model of pre-eclampsia with proteinuria, hypertension and elevated endothelin (ET-1) blood levels. We describe here the cardiovascular in vivo effects of ET-1 in this rat model since ET-1 and NO are both important vasoactive mediators in uteroplacental circulation. From day 13 of gestation 2 groups of Wistar female rats were fed control (C) or nitroarginine enriched diet (0.063%, Treated: T). On gestational 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 injection (0.1 nmol/kg) is rapidly followed by a decrease in blood pressure significantly more important in T: -46 +/- 5.1 than in C: -30 +/- 2.2. In vivo depressor effect is blocked by the specific antagonist BQ-788. After inhibition of cycloxygenase with acetylsalicylic acid (27 mumol/kg, 30 min before) the hypotension is not modified. Since NO and PGI2 productions are not expected in our conditions, vasodepressor effect can be explained by an endothelial hyperpolarazing factor (EDHF). In conclusion in vivo ET-1 hypotensive effects in pregnant rats are mediated by ETB receptors and more pronounced in hypertensive NO-deprived animals.
Matz
R
R
Service de pharmacologie et physiopathologie cellulaires, CNRS ERS 653, Faculté de Pharmacie, Université Louis-Pasteur, Illkirch.
Van Overloop
B
B
Dieye
A M
AM
Pernot
F
F
Gairard
A
A
D000818:Animals; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007022:Hypotension / Q000139:chemically induced*; D019001:Nitric Oxide Synthase; D009842:Oligopeptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017208:Rats, Wistar
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010880:Piperidines; C086539:BQ 788; D019001:Nitric Oxide Synthase