Chronic hypoxia opposes pregnancy-induced increase in uterine artery vasodilator response to flow

Stephanie N Mateev, A. Hugo Sillau, Rhonda Mouser, Robert E. McCullough, Margueritte M. White, David A. Young, Lorna G. Moore

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

We tested the hypotheses that pregnancy increases the uterine artery (UA) vasodilator response to flow and that this increase is impaired under conditions of chronic hypoxia (30 days, simulated elevation 3,960 m). UA were isolated from 24 normoxic or chronically hypoxic midpregnant guinea pigs and studied with the use of pressure myography. Normoxic pregnancy increased UA flow vasodilator response and protected against a rise in wall shear stress (WSS). Chronic hypoxia opposed these effects, prompting vasoconstriction at high flow and increasing WSS above levels seen in normoxic pregnant UA. The nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NNA) eliminated the pregnancy-associated increase in flow vasodilation in normoxic UA, suggesting that increased nitric oxide production was responsible. The considerable residual vasodilation after nitric oxide synthase and cyclooxygenase inhibition implicated endothehal-derived hyperpolarizing factor (EDHF) as an additional contributor to flow vasodilation. L-NNA increased flow vasodilation in UA from chronically hypoxic animals, suggesting that chronic hypoxia may have lowered EDHF or elevated peroxynitrite production. In conclusion, flow is an important physiological vasodilator for the acute and more chronic UA dimensional changes required to increase uteroplacental blood flow during normal pregnancy. Chronic hypoxia may be a mechanism that opposes the pregnancy-associated rise in UA flow vasodilation, thereby increasing the incidence of preeclampsia and intrauterine growth restriction at a high altitude.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number3 53-3
StatePublished - Mar 1 2003
Externally publishedYes

Keywords

  • Acetylcholine
  • Endothelium-derived hyperpolarizing factor
  • Nitric oxide
  • Peroxynitrites
  • Preeclampsia

ASJC Scopus subject areas

  • Physiology

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