Atrial natriuretic peptide increases inflammation, infarct size, and mortality after experimental coronary occlusion
- 1 March 2009
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Heart and Circulatory Physiology
- Vol. 296 (3), H655-H661
- https://doi.org/10.1152/ajpheart.00684.2008
Abstract
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.Keywords
This publication has 45 references indexed in Scilit:
- The Many Possible Benefits of Natriuretic Peptides After Myocardial InfarctionHypertension, 2005
- Role of Natriuretic Peptide Receptor Guanylyl Cyclase-A in Myocardial Infarction Evaluated Using Genetically Engineered MiceHypertension, 2005
- Determinants of natriuretic peptide gene expressionPeptides, 2005
- Equimolar doses of atrial and brain natriuretic peptides and urodilatin have differential renal actions in overt experimental heart failureAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005
- Effects of angiotensin II receptor blockade versus angiotensin-converting-enzyme inhibition on ventricular remodelling following myocardial infarction in the mouseClinical Science, 2003
- Plasma levels of atrial natriuretic peptide and tumor necrosis factor-α during transient myocardial ischemia in patients with stable anginaKlinische Wochenschrift, 1991
- Attenuation of neutrophil function by inhibitors of arachidonate metabolism reduces the extent of canine myocardial infarctionThe American Journal of Cardiology, 1989
- Potentiation of platelet aggregation by atrial natriuretic peptideLife Sciences, 1988
- Effects of atrial natriuretic factor on human platelet functionLife Sciences, 1985
- Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog.Circulation, 1983