Endothelium and aortic contraction to endothelin-1 in the pregnant rat

Endothelium-derived factors modulate tone and may be involved in hyporeacti vity to vasoconstrictors, such as norepinephrine or angiotensin II, as has been previously described during gestation. The endothelium produces endoth elin-1, a major vasoconstrictor peptide, therefore aortic contractions to e ndothelin-1 (10(-10) to 3 x 10(-7) M) were used to assess the role of the e ndothelium in pregnant Wistar rats (at 20 days of gestation). Late pregnanc y is characterized by a significantly diminished systolic blood pressure in conscious rats (-17 mmHg, P < 0.001, n = 14). In pregnant and in age-match ed nonpregnant female rats, endothelin-1 induced aortic contraction was gre ater when endothelium was present (at least P < 0.01). Indomethacin signifi cantly reduced this contraction in aortic rings with intact endothelium in all groups. In aortic rings that had endothelium physically removed, contra ction 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 cycloox ygenases in vascular smooth muscle during pregnancy. In vessels with intact endothelium, we did not find hyporeactivity to endothelin-1 during late pr egnancy. Contraction to endothelin-1 involved ETA receptors because it was decreased by BQ-123, an ETA receptor antagonist, whereas there was no signi ficant change when using BQ-788, an ETB receptor antagonist.