Contribution of endogenous endothelin-1 to basal vascular tone during normal pregnancy and preeclampsia.
OBJECTIVE
The aim of this study was to determine the physiologic role for endogenous endothelin in the regulation of vascular tone during normal pregnancy and preeclampsia. The vascular sensitivity to endothelin-1 during pregnancy was studied also.


METHODS
Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of phosphoramidon, an endothelin-converting enzyme inhibitor, for 60 minutes, which was followed by co-infusion with endothelin-1 for 30 minutes. Three groups were studied: healthy nonpregnant women, normal pregnant women, and women with preeclampsia.


RESULTS
There was a significant increase in forearm blood flow in the nonpregnant group after phosphoramidon infusion alone (73%+/-37%; P<.05). Phosphoramidon did not change forearm blood flow in pregnant subjects. Co-infusion with endothelin-1 significantly decreased forearm blood flow in both the nonpregnant and normal pregnant women (53%+/-7% and 40%+/-11%, respectively; P<.01). No response to endothelin-1 was found among women with preeclampsia.


CONCLUSIONS
The vascular sensitivity to endothelin-1 is not altered during normal pregnancy in contrast to preeclamptic pregnancy, where no effect of endothelin-1 was seen. Reduced endothelin dependence during pregnancy might be one mechanism behind the fall in peripheral vascular resistance.
Ajne
G
G
Department of Obstetrics, Karolinska University Hospital Huddinge, Karolinska Institute, Stockholm, Sweden. gunilla.ajne@karolinska.se
Ahlborg
G
G
Wolff
K
K
Nisell
H
H
D000328:Adult; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000378:metabolism* / Q000494:pharmacology; D000072396:Endothelin-Converting Enzymes; D005260:Female; D005542:Forearm / Q000098:blood supply; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D011480:Protease Inhibitors / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D014666:Vasomotor System / Q000503:physiopathology*
D019332:Endothelin-1; D006020:Glycopeptides; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon