Mechanisms of endothelium-dependent relaxation in myometrial resistance vessels and their alteration in preeclampsia.
OBJECTIVE
To investigate the importance of prostacyclin and nitric oxide synthesis in endothelium-dependent relaxation in myometrial resistance vessels, and to test the hypothesis that a deficiency in nitric oxide synthesis contributes to the known alterations in endothelial function in preeclampsia.


METHODS
Thirty-six women with normal pregnancies and 14 with preeclampsia had the myometrium biopsied at cesarean section. Resistance arteries were dissected and mounted on a wire myograph. After preconstriction with vasopressin, vessels were treated cumulatively with bradykinin. The process was repeated in the presence of indomethacin and then indomethacin and NG-monomethyl-L-arginine (L-NMMA).


RESULTS
The vessels from women with normal pregnancies showed endothelium-dependent relaxation to bradykinin which was not significantly altered by the presence of indomethacin. The addition of L-NMMA significantly, but only partially, reduced the relaxation to bradykinin in the presence of indomethacin (p = 0.03). The vessels from women with preeclampsia showed markedly reduced relaxation to bradykinin (p < 0.0001), as compared to vessels from normal pregnant women. Relaxation of vessels from women with preeclampsia was increased by the addition of indomethacin (p = 0.03) but was virtually eradicated by the presence of L-NMMA.


CONCLUSIONS
Eicosanoid synthesis plays little part in the relaxation of normal pregnant myometrial vessels to bradykinin. Nitric oxide synthesis mediates part but not all of the endothelium-dependent relaxation. In preeclampsia, relaxation to bradykinin is reduced; inhibition of eicosanoid synthesis allows increased relaxation, and nitric oxide synthesis appears to mediate a greater proportion of the relaxation than in normal pregnant women.
Ashworth
J R
JR
Department of Obstetrics and Gynaecology, City Hospital, Nottingham, United Kingdom.
Baker
P N
PN
Warren
A Y
AY
Johnson
I R
IR
D000328:Adult; D001920:Bradykinin / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009215:Myometrium / Q000098:blood supply*; D011225:Pre-Eclampsia / Q000503:physiopathology*; D011247:Pregnancy; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001920:Bradykinin; D007213:Indomethacin