Endothelium and aortic contraction to endothelin-1 in the pregnant rat.
Endothelium-derived factors modulate tone and may be involved in hyporeactivity to vasoconstrictors, such as norepinephrine or angiotensin II, as has been previously described during gestation. The endothelium produces endothelin-1, a major vasoconstrictor peptide, therefore aortic contractions to endothelin-1 (10(-10) to 3 x 10(-7) M) were used to assess the role of the endothelium in pregnant Wistar rats (at 20 days of gestation). Late pregnancy is characterized by a significantly diminished systolic blood pressure in conscious rats (-17 mmHg, P < 0.001, n = 14). In pregnant and in age-matched nonpregnant female rats, endothelin-1 induced aortic contraction was greater when endothelium was present (at least P < 0.01). Indomethacin significantly reduced this contraction in aortic rings with intact endothelium in all groups. In aortic rings that had endothelium physically removed, contraction to endothelin-1 was greater in pregnant rats than in nonpregnant ones. Indomethacin decreased contraction of aortic rings in pregnant rats only. These results suggest an enhanced synthesis of vasoconstrictors by cyclooxygenases in vascular smooth muscle during pregnancy. In vessels with intact endothelium, we did not find hyporeactivity to endothelin-1 during late pregnancy. Contraction to endothelin-1 involved ET(A) receptors because it was decreased by BQ-123, an ET(A) receptor antagonist, whereas there was no significant change when using BQ-788, an ET(B) receptor antagonist.
Dièye
A M
AM
Pharmacologie et Physico-Chimiedes Interactions Cellulaires et Moléculaires, Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France.
Gairard
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects; D014757:Viper Venoms / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; D014757:Viper Venoms; C057354:sarafotoxins s6; C086539:BQ 788; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin