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

Jakovljevic, V.Lj. and Canovic, P.S. and Andjelkovic, N.V. and Djuric, D.M. (2006) The effects of nimodipine and L-NAME on coronary flow and oxidative stress parameters in isolated rat heart. Acta Physiologica Hungarica, 93 (4). pp. 251-261. ISSN 0231-424X

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Abstract

The aim of this study was to assess the eff ects of Ca 2+ 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 H 2 O). The experiments were performed under control conditions, in the pre sence of Nimodipine (2μM) or Nimodipine (2μM) plus L -NAME (30μM). Coronary flow (CF) varied in the autoregulatory range from 3.7±0.4ml/min/g wt at 50cm H2O to 4.35±0.79 at 90cm H2O. Basal nitrite outflow, index of lipid peroxidation (measured as TBAR S release) and superoxide anion release (O2–) (at 60cm H2O) were 0.64±0.18nmol/min/g wt, 0.55±0.13μmol/min/g wt and 19.72±3.70nmol/min/g wt, respectively. Nimodipine induced significant vasodilation at all values of CPP (from 26% at 40 cm H 2 O to 36% at 120 cm H 2 O) accompanied with significant decrease of nitrite outflow (from 59% at 40 cm H 2 O to 40% at 120 cm H 2 O), significant increase of TBARS above autoregulatory range (about 40%) and significant increase of O 2 – release (from 186% at 40 cm H 2 O to 117% at 120 cm H 2 O). 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 H 2 O to 11% at 120 cm H 2 O) without changes in the autoregulatory range, accompanied with significantly increased nitrite outflow (from 69% at 40 cm H 2 O to 36% at 120 cm H 2 O) and TBARS release (almost 50%), as well as significantly decreased O 2 – release (from 50% at 40 cm H 2 O to 43% at 120 cm H 2 O). Our findings show that effect of nimodipi ne on coronary flow should be significantly influenced by NO, TBARS and O 2 – release in isolated rat heart.

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