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Prolonged Uterine Artery Nitric Oxide Synthase Inhibition Modestly Alters Basal Uteroplacental Vasodilation in the Last Third of Ovine Pregnancy.
MedLine Citation:
PMID:  25128169     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of involvement is unclear. Bolus intra-arterial infusions of L-nitro-arginine methyl ester (L-NAME) modestly decrease ovine basal UPBF; however, the doses and duration of infusion may have been insufficient. We, therefore, examined prolonged uterine artery (UA) NO synthase inhibition with L-NAME throughout the last third of ovine pregnancy, performing either continuous 30min UA infusion dose-responses (n=4) or 72h UA infusions (0.01 mg/ml) at 104-108, 118-125 and 131-137d of gestation (n=7) while monitoring mean arterial pressure (MAP), heart rate (HR) and UPBF. Uteroplacental vascular resistance (UPVR) was calculated and uterine cGMP synthesis measured. Thirty minute UA L-NAME infusions did not dose-dependently decrease UPBF, increase UPVR or decrease uterine cGMP synthesis (P>0.1); however, MAP rose and HR fell modestly. Prolonged continuous 72h UA L-NAME infusions decreased UPBF ~32%, increased UPVR ~68% (P≤0.001) and decreased uterine cGMP synthesis 70% at 54-72h (P≤0.004); the noninfused uterine horn was unaffected. This was associated with ~10% increases in MAP and decreases in HR that were greater at 104-108d vs. 118-125 and 131-137d gestation (P=0.006). Although uterine and UA NO and cGMP synthesis increase several fold during ovine pregnancy, they contribute modestly to the maintenance and rise in UPBF in the last third of gestation. Thus, local UA NO may primarily modulate vasoconstrictor responses. Notably, the systemic vasculature appears more sensitive to NOS inhibition than the uterine.
Authors:
Charles R Rosenfeld; Timothy Roy
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-15
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013, American Journal of Physiology - Heart and Circulatory Physiology.
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