Prolonged uterine artery nitric oxide synthase inhibition modestly alters basal uteroplacental vasodilation in the last third of ovine pregnancy

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Abstract

Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but they likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro-L-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 by performing either continuous 30-min UA infusion dose responses (n = 4) or 72-h UA infusions (0.01 mg/ml) at 104–108, 118–125, and 131–137 days 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 was 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 72-h UA L-NAME infusions decreased UPBF ∼32%, increased UPVR ∼68% (P ≤ 0.001), and decreased uterine cGMP synthesis 70% at 54–72 h (P ≤ 0.004); the noninfused uterine horn was unaffected. These findings were associated with ∼10% increases in MAP and decreases in HR that were greater at 104–108 than 118–125 and 131–137 days of gestation (P = 0.006). Although uterine and UA NO and cGMP synthesis increase severalfold 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 than the uterine vasculature to NO synthase inhibition.

Original languageEnglish (US)
Pages (from-to)H1196-H1203
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume307
Issue number8
DOIs
StatePublished - Oct 15 2014

Fingerprint

Uterine Artery
Vasodilation
Nitric Oxide Synthase
Sheep
NG-Nitroarginine Methyl Ester
Pregnancy
Vascular Resistance
Arterial Pressure
Nitric Oxide
Heart Rate
Intra Arterial Infusions
Vasoconstrictor Agents
Maintenance

Keywords

  • CGMP synthesis
  • Mean arterial pressure
  • Nitric oxide synthase inhibition
  • Sheep
  • Uteroplacental blood flow

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

@article{5e7239229639481f8fa9e666ed82b57e,
title = "Prolonged uterine artery nitric oxide synthase inhibition modestly alters basal uteroplacental vasodilation in the last third of ovine pregnancy",
abstract = "Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but they likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro-L-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 by performing either continuous 30-min UA infusion dose responses (n = 4) or 72-h UA infusions (0.01 mg/ml) at 104–108, 118–125, and 131–137 days 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 was 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 72-h UA L-NAME infusions decreased UPBF ∼32{\%}, increased UPVR ∼68{\%} (P ≤ 0.001), and decreased uterine cGMP synthesis 70{\%} at 54–72 h (P ≤ 0.004); the noninfused uterine horn was unaffected. These findings were associated with ∼10{\%} increases in MAP and decreases in HR that were greater at 104–108 than 118–125 and 131–137 days of gestation (P = 0.006). Although uterine and UA NO and cGMP synthesis increase severalfold 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 than the uterine vasculature to NO synthase inhibition.",
keywords = "CGMP synthesis, Mean arterial pressure, Nitric oxide synthase inhibition, Sheep, Uteroplacental blood flow",
author = "Rosenfeld, {Charles R.} and Timothy Roy",
year = "2014",
month = "10",
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doi = "10.1152/ajpheart.00996.2013",
language = "English (US)",
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pages = "H1196--H1203",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
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T1 - Prolonged uterine artery nitric oxide synthase inhibition modestly alters basal uteroplacental vasodilation in the last third of ovine pregnancy

AU - Rosenfeld, Charles R.

AU - Roy, Timothy

PY - 2014/10/15

Y1 - 2014/10/15

N2 - Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but they likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro-L-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 by performing either continuous 30-min UA infusion dose responses (n = 4) or 72-h UA infusions (0.01 mg/ml) at 104–108, 118–125, and 131–137 days 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 was 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 72-h UA L-NAME infusions decreased UPBF ∼32%, increased UPVR ∼68% (P ≤ 0.001), and decreased uterine cGMP synthesis 70% at 54–72 h (P ≤ 0.004); the noninfused uterine horn was unaffected. These findings were associated with ∼10% increases in MAP and decreases in HR that were greater at 104–108 than 118–125 and 131–137 days of gestation (P = 0.006). Although uterine and UA NO and cGMP synthesis increase severalfold 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 than the uterine vasculature to NO synthase inhibition.

AB - Mechanisms regulating uteroplacental blood flow (UPBF) in pregnancy remain unclear, but they likely involve several integrated signaling systems. Endothelium-derived nitric oxide (NO) is considered an important contributor, but the extent of its involvement is unclear. Bolus intra-arterial infusions of nitro-L-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 by performing either continuous 30-min UA infusion dose responses (n = 4) or 72-h UA infusions (0.01 mg/ml) at 104–108, 118–125, and 131–137 days 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 was 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 72-h UA L-NAME infusions decreased UPBF ∼32%, increased UPVR ∼68% (P ≤ 0.001), and decreased uterine cGMP synthesis 70% at 54–72 h (P ≤ 0.004); the noninfused uterine horn was unaffected. These findings were associated with ∼10% increases in MAP and decreases in HR that were greater at 104–108 than 118–125 and 131–137 days of gestation (P = 0.006). Although uterine and UA NO and cGMP synthesis increase severalfold 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 than the uterine vasculature to NO synthase inhibition.

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KW - Mean arterial pressure

KW - Nitric oxide synthase inhibition

KW - Sheep

KW - Uteroplacental blood flow

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