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

In pregnant rats during hypertension induced by NO synthase inhibition, endothelin (ET) plasma levels are increased as in some preeclamptic women. Previously, 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) were 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, measured by the tail cuff method on conscious rats at day 20 of gestation, was raised by the chronic L-NNA treatment (mean +/- s.e.m., mmHg, p < 0.001: pregnant L-NNA treated, 145 +/- 1.84 vs. pregnant control, 101 +/- 2.00 and non-pregnant 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 previously precontracted with norepinephrine only when endothelium was present. In control rats, ET-1 (10(-8) to 5 x 10(-8) M) produced a short but significant relaxation (mean value between 4 to 19%) followed by a long-lasting contracting phase, and a higher ET-1 concentration (10(-7) M) only produced 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-NAME (10(-4) M) preincubation, relaxation was completely inhibited in non-pregnant and pregnant rats. BQ-123, an ETA receptor antagonist, did not produce any effect on ET-1 induced relaxation. BQ-788, an ETB 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 involves endothelial ETB receptors. Despite a decrease in the systemic vascular reactivity during late gestation, the vasodilating and vasoconstricting properties of ET-1 on the aorta are not changed.