Increased nitric oxide synthase activity and expression in the human uterine artery during pregnancy.
Evidence exists that NO plays a role in the vasodilation that occurs during pregnancy. The purpose of the present study was to determine whether the role of NO is associated with an increase in the activity and protein expression of NO synthase (NOS) in the human uterine artery. Uterine arteries were obtained from pregnant patients (P arteries) and nonpregnant patients (NP arteries). NOS activity was estimated with the L-[(3)H]-arginine-to-L-[(3)H]-citrulline conversion method and on the basis of changes in tissue levels of cGMP. Western immunoblotting and immunohistochemistry were used to assess NOS protein expression. Ca(2+)-dependent NOS activity was 8 times greater (P:<0.01) in P than in NP arteries. Although most of this pregnancy-induced increase in NOS activity was Ca(2+) dependent (64%), a considerable portion was Ca(2+) independent. Expressions of endothelial NOS (eNOS) and neuronal NOS, but not inducible NOS, were demonstrated in P and NP arteries. The eNOS was located in the endothelium and stained with a qualitative order of P arteries>NP arteries (follicular)>NP arteries (luteal). The neuronal NOS was located in the adventitia of P and NP arteries. Basal NO-dependent and bradykinin-stimulated levels of cGMP were higher (P:<0.05) in P than in NP arteries. These results indicate that an upregulation of eNOS protein expression could account for the increased NO synthesis/release in the human uterine artery during pregnancy.
Nelson
S H
SH
Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555, USA. snelson@utmb.edu
Steinsland
O S
OS
Wang
Y
Y
Yallampalli
C
C
Dong
Y L
YL
Sanchez
J M
JM
D000328:Adult; D001120:Arginine / Q000032:analysis; D001158:Arteries / Q000378:metabolism*; D015153:Blotting, Western; D002122:Calcium Chloride; D002147:Calmodulin; D006152:Cyclic GMP / Q000032:analysis; D004492:Edetic Acid; D004730:Endothelium, Vascular / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III; D011247:Pregnancy / Q000378:metabolism*; D015854:Up-Regulation; D014599:Uterus / Q000098:blood supply* / Q000294:innervation; D014664:Vasodilation
D002147:Calmodulin; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D004492:Edetic Acid; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP; D002122:Calcium Chloride; D019331:NG-Nitroarginine Methyl Ester