Loss of nitric oxide synthase contributes to endothelial dysfunction in reperfused hearts

R. Giraldez, A. Panda, J. Zweier

Research output: Contribution to journalArticlepeer-review

Abstract

Endothelium-dependent relaxation (EDR) is impaired after myocardial reperfusion (R). This may be due to altered nitric oxide formation from endothelial nitric oxide synthase (eNOS). However, the role of eNOS alterations in impaired EDR of postischemic (PI) hearts is unknown. Thus, correlative studies of eNOS activity and EDR were performed in isolated rat hearts (n=35) subjected to 30 to 120 min of global no-flow ischemia (I) followed by R. eNOS activity was measured using the 14C-arginine to 14C-citrulline conversion assay Coronary flow (CF) was monitored and the effects of histamine (10-4M) and L-NAME (1mM) tested. Western-blots (WB) and immunohistology (IH) of eNOS in the heart tissue were performed to detect changes in the amount of the enzyme. While eNOS activity was unchanged after 30 min of I, it rapidly decreased thereafter with almost complete loss after 120 min. Reperfusion was associated with partial but significant recovery of eNOS activity. After 30 min of I, L-NAME infusion caused 30% decrease in CF similar to nonI control hearts whereas after 60 or 90 min it resulted in only 17 of 10% reduction of CF, respectively. Histamine-induced vasodilation paralleled changes noted for L-NAME. WB and IH revealed a progressive decrease of eNOS associated with with longer periods of I. Thus, eNOS activity was decreased in the PI heart with diminished amounts of enzyme and this correlated with impairment in EDR.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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