Hypotensive effect of endothelin-1 in nitric oxide-deprived, hypertensive pregnant rats.
Both nitric oxide (NO) and endothelin-1 (ET-1) are important mediators in the regulation of vascular tone during pregnancy and preeclampsia. This study was designed to investigate the ET-1-induced hypotensive effect in late pregnant rats (P) and in NO-deprived hypertensive pregnant rats (TP), a model 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 (MAP +/- SEM, in mm Hg) and heart rate (HR) were measured with a carotid catheter in anesthetized rats after a bolus intravenous injection of several agonists and antagonists. After 7 days of chronic NO synthase inhibition, there was a significant increase in MAP (+45 +/- 3.9, P < .01) and 24-h urinary nitrate excretion was significantly decreased (P < .05). ET-1 bolus injection (0.1 nmol/kg) was rapidly followed by a significant decrease in MAP and a slight delayed increase, with no change in HR. The magnitude of the decrease 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 specific ETB agonist, and blocked by the specific ETB antagonist BQ-788. After inhibition of cyclooxygenase with acetylsalicylic acid, the ET-1-induced hypotension 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 magnitude of the hypotensive effect of ET-1 observed in TP is of the same order as that in virgin rats and neither NO nor vasodilator prostaglandins seem to be involved in TP. The enhanced hypotensive effect of ET-1 could be a beneficial counter-balancing mechanism in this rat model of preeclamptic pathology where an increased sensitivity to vasoconstrictor agents is generally described.
Matz
R L
RL
Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, CNRS UMR 7034, Faculté de Pharmacie, Université Louis Pasteur, Illkirch, France.
Van Overloop
B
B
Gairard
A
A
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D007022:Hypotension / Q000139:chemically induced*; D009569:Nitric Oxide / Q000172:deficiency*; D011225:Pre-Eclampsia / Q000503:physiopathology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000187:drug effects
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D009569:Nitric Oxide