Enhanced β‐adrenergic response in rat papillary muscle by inhibition of inducible nitric oxide synthase after myocardial infarction

Abstract

Myocardial infarction (MI) induces a progressive ventricular remodelling leading to a contractility depression. During the acute phase of MI inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production increases in the heart. The aim of this study was to investigate the role of iNOS in the left ventricular contractility at 3 days after MI. Wistar rats were divided into: sham operated (SHAM, n = 23), infarction (INF, n = 18); sham operated plus the iNOS inhibitor, S-methylisothiourea (SMT) 5 mg kg(-1) day(-1), i.p. treatment (SHAM-SMT, n = 26) and infarction plus SMT (INF-SMT, n = 22). Concentration-response curves for isoprenaline, Ca(2+) and frequency-force curve were studied in isolated papillary muscle from left ventricle. After 3 days infarct area was similar between groups. SMT treatment reduced the time to peak tension during frequency-force curve in the infarct group (SHAM = 63 +/- 3; SHAM-SMT = 71 +/- 3; INF = 90 +/- 4; INF-SMT = 79 +/- 4 ms, P < 0.05) and increased the maximal response to isoprenaline (SHAM = 0.93 +/- 0.11; SHAM-SMT = 1.13 +/- 0.1; INF =0.84 +/- 0.16; INF-SMT = 1.49 +/- 0.15 g mm(-2), P < 0.05). The response to Ca(2+) was equally reduced in the INF and INF-SMT groups. SMT treatment did not change the reduced post-rest potentiation performed by INF group, but attenuated the plasma nitrite and nitrate (NOx) levels in the INF group without any haemodynamic effect. These finding suggest that at 3 days after MI the iNOS modulates the isolated papillary muscle response to isoprenaline and its inhibition improves the beta-adrenergic inotropic responses.