The effects of nimodipine and L-NAME on coronary flow and oxidative stress parameters in isolated rat heart

Abstract

The aim of this study was to assess the effects of Ca2+ channel antagonist nimodipine (in concentration which competitive inhibited phosphodiesterase 1 - PDE1) on oxidative stress alone or under inhibition of nitric oxide synthase by L-NAME in isolated rat heart. The hearts from male Wistar albino rats (n=18, BM about 200 g, age 8 weeks) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure conditions (CPP, 40-120 cm H2O). The experiments were performed under control conditions, in the presence of Nimodipine (2 μM) or Nimodipine (2 μM) plus L-NAME (30 μM). Coronary flow (CF) varied in the autoregulatory range from 3.7±0.4 ml/min/g wt at 50 cm H2O to 4.35±0.79 at 90 cm H2O. Basal nitrite outflow, index of lipid peroxidation (measured as TBARS release) and superoxide anion release (O2-) (at 60 cm H2O) were 0.64±0.18 nmol/min/g wt, 0.55±0.13 μmol/min/g wt and 19.72±3.70 nmol/min/g wt, respectively. Nimodipine induced significant vasodilation at all values of CPP (from 26% at 40 cm H2O to 36% at 120 cm H2O) accompanied with significant decrease of nitrite outflow (from 59% at 40 cm H2O to 40% at 120 cm H2O), significant increase of TBARS above autoregulatory range (about 40%) and significant increase of O2-release (from 186% at 40 cm H2O to 117% at 120 cm H2O). However, perfusion with L-NAME completely reversed the effects of Nimodipine. Nimodipine-induced flow changes were decreased under L-NAME (from 3 % at 40 cm H2O to 11% at 120 cm H2O) without changes in the autoregulatory range, accompanied with significantly increased nitrite outflow (from 69% at 40 cm H2O to 36% at 120 cm H2O) and TBARS release (almost 50%), as well as significantly decreased O2 -release (from 50% at 40 cm H2O to 43% at 120 cm H2O). Our findings show that effect of nimodipine on coronary flow should be significantly influenced by NO, TBARS and O2-release in isolated rat heart. © 2006 Akadémiai Kiadó, Budapest.