Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs

David B. Pearse, Patrice M. Becker

Research output: Contribution to journalArticlepeer-review

Abstract

We previously found that increased intravascular pressure decreased ischemic lung injury by a nitric oxide (NO)-dependent mechanism (Becker PM, Buchanan W, and Sylvester JT. J Appl Physiol 84: 803-808, 1998). To determine the role of cyclic nucleotides in this response, we measured the reflection coefficient for albumin (σ(alb)), fluid flux (J̇) cGMP, and cAMP in ferret lungs subjected to either 45 min ('short'; n = 7) or 180 min ('long') of ventilated ischemia. Long ischemic lungs had 'low' (1-2 mmHg, n = 8) or 'high' (7-8 mmHg, n = 6) vascular pressure. Other long low lungs were treated with the NO donor (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA-NONOate; 5 x 10-4 M, n = 6) or 8-bromo-cGMP (5 x 10-4 M, n = 6). Compared with short ischemia, long low ischemia decreased σ(alb) (0.23 ± 0.04 vs. 0.73 ± 0.08; P < 0.05) and increased J̇ (1.93 ± 0.26 vs. 0.58 ± 0.22 ml·min-1 · 100 g-1; P < 0.05). High pressure prevented these changes. Lung cGMP decreased by 66% in long compared with short ischemia. Lung cAMP did not change. PAPA-NONOate and 8-bromo-cGMP increased lung cGMP, but only 8-bromo-cGMP decreased permeability. These results suggest that ischemic vascular injury was, in part, mediated by a decrease in cGMP. Increased Vascular pressure prevented injury by a cGMP-independent mechanism that could not be mimicked by administration of exogenous NO.

Original languageEnglish (US)
Pages (from-to)H2077-H2084
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number5 48-5
DOIs
StatePublished - 2000

Keywords

  • Filtration Coefficient
  • Lung injury
  • Reflection coefficient
  • cAMP
  • cGMP

ASJC Scopus subject areas

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

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