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.
Dieye
A M
AM
Laboratoire de Pharmacologie et Physiopathologie Cellulaires, CNRS ERS 653, Université Louis Pasteur, Faculté de Pharmacie, Illkirch, France.
Van Overloop
B
B
Gairard
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006128:Growth / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; C086539:BQ 788; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D009638:Norepinephrine