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Endothelin‐1 and relaxation of the rat aorta during pregnancy in nitroarginine‐induced hypertension
Author(s) -
Dieye Amadou Moctar,
Overloop Bruno,
Gairard Alexis
Publication year - 1999
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1999.tb00340.x
Subject(s) - endocrinology , medicine , endothelin receptor , blood pressure , endothelin 1 , gestation , contraction (grammar) , aorta , pregnancy , vasodilation , nitroarginine , endothelium , nitric oxide synthase , nitric oxide , biology , receptor , genetics
— 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‐I 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 × 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 ET A receptor antagonist, did not produce any effect on ET‐1 induced relaxation. BQ‐788, an ET B 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 ET B 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.