Endothelin-1 and relaxation of the rat aorta during pregnancy in nitroargirmine-induced hypertension

In pregnant rats during hypertension induced by NO synthase inhibition, end othelin (ET) plasma levels are increased as in some preeclamptic women. Pre viously, the enhanced vasodepressor effect of endothelin-1 (ET-1) has been observed in this model, thus we decided to study the relaxation induced by ET-1 on the aorta. Non-pregnant or pregnant Wistar rats (n = 7 by group) we re fed for 7 days (day 13-day 20) on a nitroarginine-enriched diet (L-NNA, 0.063% i.e. 30 mg/kg/day) or a control diet. Systolic blood pressure, measu red by the tail cuff method on conscious rats at day 20 of gestation, was r aised by the chronic L-NNA treatment (mean s.e.m., mmHg, p < 0.001: pregnan t L-NNA treated, 145 +/- 1.84 vs. pregnant control, 101 +/- 2.00 and non-pr egnant L-NNA treated, 148 +/- 3.11 vs. non-pregnant control, 119 +/- 1.80). On day 20 ex vivo aortic ring relaxation was produced by ET-1 in vessels p reviously precontracted with norepinephrine only when endothelium was prese nt. In control rats, ET-1 (10(-8) to 5 x 10(-8) M) produced a short but sig nificant relaxation (mean value between 4 to 19%) followed by a long-lastin g contracting phase, and a higher ET-1 concentration (10(-7) M) only produc ed contraction. Chronic L-NNA treatment decreased the level of relaxation ( at least p < 0.05, in non-pregnant and pregnant rats) and with a 30 min L-N AME (101 M) preincubation, relaxation was completely inhibited in non-pregn ant and pregnant rats. BQ-123, an ETA receptor antagonist, did not produce any effect on ET-1 induced relaxation. BQ-788, an ETA receptor antagonist, significantly decreased it. In conclusion, in female rats, as in male rats, ET-1 induces a transient relaxation in the preconstricted aorta which invo lves endothelial ETB receptors. Despite a decrease in the systemic vascular reactivity during late gestation, the vasodilating and vasoconstricting pr operties of ET-1 on the aorta are not changed. (C) Elsevier, Paris.