Hypotensive effect of endothelin-1 in nitric oxide-deprived, hypertensive pregnant rats

Both nitric oxide (NO) and endothelin-1 (ET-I) are important. mediators in the regulation of vascular tone during pregnancy and preeclampsia. This stu dy was designed to investigate the ET-l-induced hypotensive effect in late pregnant rats (P) and in NO-deprived hypertensive pregnant rats (TP), a mod el of preeclampsia. From day 13 of pregnancy Wistar rats were fed a control or an N-omega-nitro -L-arginine-enriched diet. On gestational day 20, mean arterial pressure (M AP +/- SEM, in mm Hg) and heart rate (HR) were measured with a carotid cath eter in anesthetized rats after a bolus intravenous injection of several ag onists and antagonists. After 7 days of chronic NO synthase inhibition, the re was a significant increase in MAP (+45 +/- 3.9, P < .01) and 24-h urinar y nitrate excretion was significantly decreased (P < .05). ET-1 bolus injec tion (0.1 nmol/kg) was rapidly followed by a significant decrease in MAP an d a slight delayed increase, with no change in HR. The magnitude of the dec rease had significantly dropped off in P (-30 +/- 2.2) as compared to that in TP (-46 +/- 5.1) and in virgin rats (-51 +/- 6.3) (P < .05). In P and TP , in vivo depressor effect was also obtained with sarafotoxin S6c, a specif ic ETB agonist, and blocked by the specific ETB antagonist BQ-788. After in hibition of cyclooxygenase with acetyl salicylic acid, the ET-l-induced hyp otension was not modified either in P or in TP. In conclusion, the present data highlight an enhanced ETB receptor mediated hypotensive effect of ET-1 in anesthetized TP as compared to P. The magnit ude of the hypotensive effect of ET-I observed in TP is of the same order a s that in virgin rats and neither NO nor vasodilator prostaglandins seem to be involved in TP. The enhanced hypotensive effect of ET-I could be a bene ficial counterbalancing mechanism in this rat model of preeclamptic patholo gy where an increased sensitivity to vasoconstrictor agents is generally de scribed. (C) 2001 American Journal of Hypertension, Ltd.