Repetitive myocardial stunning in pigs is associated with the increased expression of inducible and constitutive nitric oxide synthases

Objectives: Nitric oxide (NO) has complex effects on myocardial function pa rticularly following ischaemia-reperfusion. The goal of this study was to e xamine the result of repetitive myocardial stunning on myocardial NO releas e and expression of inducible (iNOS) and constitutive (eNOS) NO synthases. Methods and results: Propofol anaesthetised pigs underwent ten, 2-min episo des of circumflex artery occlusion (n=6) or acted as sham operated controls (n=4). Measurements of segment shortening demonstrated a fall in function in the ischaemic territory to 52.5 +/- 7.3% (mean+/-S.E.M.) of baseline sho rtening 30 min after the stunning stimulus, recovering to 92+/-8.7% 5.5 h l ater. Function remained stable in sham controls. The change in venous-arter ial [NO] between baseline and 6 h reperfusion was found to be significantly different between the two groups (0.2+/-0.7 in stunned vs. -4.3+/-1.6 mu M in shams; P<0.02). Western blotting and band optical density used to compa re tissue from stunned territory (S), non-stunned territory (IC) and sham c ontrol animals (SC) demonstrated this was associated with an increase in th e expression of both iNOS (S: 93+/-13.4, IC: 37+/-2.4 and SC: 25+/-4 [arbit rary units], P<0.01 and P=0.031) and eNOS (S: 104+/-7.4, IC; 62.5+/-7.4 and SC; 75.7+/-0.6, P<0.03 and P<0.01) in stunned myocardium. Immunocytochemis try localised iNOS reactivity to vascular smooth muscle cells and cardiomyo cytes in stunned tissue and eNOS reactivity to endothelial cells. Conclusio n: Recovery from repetitive myocardial stunning is associated with the incr eased expression of both iNOS and eNOS and would be compatible with a prote ctive role for both these enzymes. This finding has possible relevance for both the late window of ischaemic preconditioning and myocardial hibernatio n. (C) 1999 Elsevier Science B.V. All rights reserved.