Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling

J Appl Physiol (1985). 1993 Mar;74(3):1061-5. doi: 10.1152/jappl.1993.74.3.1061.

Abstract

We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood-perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2-5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Hypoxia / metabolism*
  • Hypoxia / physiopathology
  • In Vitro Techniques
  • Lung / metabolism*
  • Male
  • Nitric Oxide / metabolism*
  • Perfusion
  • Pulmonary Circulation / physiology
  • Rats
  • Rats, Wistar
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • omega-N-Methylarginine

Substances

  • Angiotensin II
  • omega-N-Methylarginine
  • Nitric Oxide
  • Arginine