Endothelial nitric oxide synthase is essential for postpneumonectomy compensatory vasodilation

Thomas S. Maxey, Lucas G. Fernandez, T. Brett Reece, William B. Keeling, Irving L. Kron, Victor E. Laubach

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background. After pneumonectomy, the remaining lung vasculature must vasodilate to compensate for increased blood volume. We hypothesized that endothelial nitric oxide synthase (eNOS) is essential for compensatory vasodilation after pneumonectomy. Methods. Adult, wild-type C57BL6 (WT) and eNOS knockout (eNOS-/-) mice underwent left pneumonectomy and recovered under normoxic conditions. Animals were lightly anesthetized at 1, 3, 7, or 14 days after pneumonectomy, and closed chest, systolic right ventricular pressure (RVP) was recorded using fine-needle cannulation. The right ventricle to left ventricle plus septum weight ratios were measured as an index of right ventricular hypertrophy. Two additional groups of mice (WT and eNOS-/-) were recovered after pneumonectomy in inhaled nitric oxide (iNO, 10 ppm), and RVP was measured on day 7. Results. The eNOS-/- mice had significantly higher preoperative RVP than did WT (17.1 ± 0.4 versus 14.2 ± 0.2 cmH2O, p = 0.001). Both groups exhibited transient periods of pulmonary hypertension after pneumonectomy. On day 1, RVP was 80% above baseline in eNOS-/- mice (30.7 ± 0.8 cmH2O) versus 42% in WT mice (20.2 ± 0.7 cmH2O, p = 0.0001). The RVP returned to baseline in WT mice (16.3 ± 0.2 cmH2O) but remained significantly elevated in eNOS-/- mice (28.6 ± 0.9 cmH2O) at day 3 and at each time thereafter (p = 0.0001). The iNO significantly reduced RVP in eNOS-/- animals to 15.2 ± 0.3 cmH2O (p = 0.0001) while having no effect in WT animals. Right ventricular hypertrophy was not observed in any group. Conclusions. Pneumonectomy results in a transient increase in RVP. Under normal circumstances, these pressures return to baseline within 3 days. The eNOS-/- mice failed to display compensatory vasodilation yet could be rescued with iNO. These results suggest that eNOS is essential for postpneumonectomy compensatory vasodilation.

Original languageEnglish (US)
Pages (from-to)1234-1238
Number of pages5
JournalAnnals of Thoracic Surgery
Volume81
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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