Endothelial-derived relaxing factor released by endothelial cells of human umbilical vessels and its impairment in pregnancy-induced hypertension.
The principal objective of this study was to determine and compare the capability of human umbilical vessels of normal and pregnancy-induced hypertensive parturients to produce and to release the endothelial-derived relaxing factor. A bolus of bradykinin injected in the perfusion system of human umbilical vessels induces a release of a relaxant factor, detectable by bioassay, that is pharmacologically similar to the endothelial-derived relaxing factor. Human umbilical cords were collected from normal and pregnancy-induced hypertensive parturients. In the latter group the release of endothelial-derived relaxing factor is extremely reduced. In fact, in umbilical vessels collected from normal parturients, bradykinin at a dose of 20 pmol produces a release of endothelial-derived relaxing factor equivalent to a relaxation induced by 59.9 +/- 11.0 and 30.8 +/- 11.4 pmol of glyceryl trinitrate for the artery and vein, respectively. The same dose of bradykinin in umbilical vessels, collected from pregnancy-induced hypertensive parturients, produces a release equivalent to 6.6 +/- 2.2 and 5.7 +/- 3.5 pmol of glyceryl trinitrate equivalent for the artery and vein, respectively. Neither an increasing bolus of exogenous bradykinin or an infusion of superoxide dismutase or L-arginine was able to restore the production of endothelial-derived relaxing factor to normal levels. Our results indicate a probable alteration of endothelial cell numbers or an alteration of the enzymatic pathway, probably due to cytotoxic endogenous factors produced in pregnancy.
Pinto
A
A
Department of Experimental Pharmacology, University of Naples, Italy.
Sorrentino
R
R
Sorrentino
P
P
Guerritore
T
T
Miranda
L
L
Biondi
A
A
Martinelli
P
P
D000818:Animals; D001681:Biological Assay / Q000379:methods; D001920:Bradykinin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion / Q000379:methods; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000503:physiopathology*; D011817:Rabbits; D014469:Umbilical Arteries / Q000187:drug effects / Q000378:metabolism*; D014471:Umbilical Veins / Q000187:drug effects / Q000378:metabolism*
D009569:Nitric Oxide; D001920:Bradykinin