Acute coronary artery occlusion triggers the release of atrial natriuretic peptide (ANP) from the heart. ANP affects vasodilation, natriuresis, and inflammation, but the integrated biological effects of ANP on myocardial infarction are unknown. To elucidate these effects, the left anterior coronary artery was ligated in anesthetized, ANP-deficient (ANP -/-) and congenic wild-type (ANP +/+) mice. The survival of ANP -/- mice was markedly better (56%) at 30 days postinfarction than the survival of ANP +/+ mice (20%, P < 0.01). Surviving mice were comparable initially, but ANP -/- mice developed more cardiac hypertrophy (P < 0.001) and had lower contractility indexes 30 days after infarction (P < 0.05). An analysis 24 h after coronary occlusion showed that ANP -/- mice had smaller infarcts than ANP +/+ mice (62.6 ±; 12.1 vs. 100.8 ±; 3.8%, P < 0.001) adjusted for comparable areas at risk for ischemia. The administration of ANP to ANP -/- mice via osmotic minipumps significantly enlarged infarct size to levels comparable with those observed in ANP +/+ mice (P < 0.05). There was no difference in neutrophil migration into the noninfarcted myocardium of ANP -/- mice undergoing actual versus sham-operated coronary occlusion. By comparison, after coronary occlusion, the neutrophil infiltration into the myocardium was enhanced in ANP +/+ (P < 0.0005) and ANP -/- mice administered ANP (P < 0.0005). The expression of P-selectin, a molecule that mediates neutrophil adhesion, was significantly greater after coronary occlusion in the vasculature of ANP +/+ or ANP -/- mice treated with ANP than in ANP -/- mice (P < 0.002). Taken together, these results indicate that ANP increases P-selectin, neutrophil infiltration, infarct size, and mortality following experimental coronary occlusion.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Mar 1 2009|
- Myocardial infarction
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)