Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, C92
Myocardial infarction induces an increment in nitric oxide modulation in rat coronary arteries
G. K. Couto1, L. R. Britto1, J. G. Mill2, L. V. Rossoni1
1. Physiology and Biophysics, University of Sao Paulo, S?o Paulo, S?o Paulo, Brazil. 2. Centre for Biomedical Sciences, Federal University of Espirito Santo, Vit?ria, Espirito Santo, Brazil.
Although several studies have been developed to assess the vascular function in heart failure post-myocardial infarction (MI), a few manuscripts evaluate this parameter in arteries from rats with MI without heart failure. Thus, the aim of the present study was to assess the function of isolated rat coronary arteries (CA) 4 weeks after MI. Male Wistar rats were submitted to left coronary artery ligation to produce MI (INF; n=19) or sham operation (SHAM; n=21). After 4 weeks, animals were anesthetized for measurements of arterial and left ventricular (LV) hemodynamic parameters. Only LV end-diastolic pressure values were significatively increased in INF (INF: 10.7 ± 0.6 vs. SHAM: 8.0 ± 0.3 mmHg; P<0.05). The heart chambers were separated and weighted to evaluate the hypertrophy index and INF showed a right ventricular hypertrophy (47%; P<0.05), without changes in LV weight. Afterwards, the infarction size was evaluated as a percentage of LV area by planimetry and INF exhibited 31 ± 1.4% of infarction size. To evaluate the presence of pulmonary and hepatic congestion we analyzed the humid/ dry weight ratio of these organs, and no difference was observed in these parameters between groups. The septal CA were then mounted on a wire myograph, normalised and equilibrated for 30 min in Krebs solution. Contractile viability was assessed by exposures to high K+ solution (KCl 120mM). After that, the concentration-response curves to serotonin (5-HT, 10ηM-100μM), acetylcholine (ACh, 100ρM-100μM), isoproterenol (ISO, 100ρM-30μM) or sodium nitroprusside (SNP, 100ρM-30μM) were evaluated. There was no difference in the 5-HT- or KCl-induced contraction in CA between groups. However, the endothelium-dependent relaxation induced by ACh was increased in CA from INF as compared to SHAM (pD2; INF: 6.6 ± 0.1 vs. SHAM: 6.1 ± 0.2; P<0.05), while SNP-induced endothelium-independent relaxation did not change. Additionally, a larger ISO-induced relaxation was observed in INF (Emax; INF: 92± 1.4 vs. SHAM: 83 ± 2.0% of relaxation; P<0.05). To evaluate the NO production we used the 4,5-diaminofluorescein diacetate (DAF-2) technique in transverse sections from CA before and after stimulation with ACh (1μM) or ISO (10μM). In line with our functional studies, CA from INF showed a greater increase of NO production after ACh (INF: 32 vs. SHAM: 21% of basal NO; P<0.05) or ISO (INF: 48 vs. SHAM: 32% of basal NO; P<0.05) than SHAM. The endothelial function and the beta-adrenergic response are increased in CA from rats after 4 weeks post-MI without heart failure by an enhancement of endothelial NO release. Thus, our data suggest that this vascular adjustment may represent a compensatory mechanism that contributes to improve perfusion in the hypertrophied heart.
Where applicable, experiments conform with Society ethical requirements