The effects of dipyridamole on coronary flow, nitrite outflow and oxidative stress during coronary autoregulation in isolated rat heart

Abstract

The effects of endothelial adenosine uptake inhibitor dipyridamole (in concentration which also inhibits PDE5) were examined on coronary flow (CF), nitrite outflow (NO 2 ), index of lipid peroxidation (measured as TBARS) and superoxide anion radical release (O 2. ) during coronary autoregulation in isolated rat heart. The hearts were excised from Wistar albino male rats (BM about 200 g, 8 weeks) and perfused with buffer at constant pressure. The NO 2. , TBARS and O 2. were estimated by spectrophotometry. The coronary autoregulation (CA) was investigated with follow-up of coronary perfusion pressure (CPP) changes from 40 to 120 cm H 2 O. After first sequence of CPP changes (basic protocol), the hearts were perfused with: a) dipyridamole (0.4 μM) alone or b) in combination with nitric oxide synthase inhibitor (L-NAME, 30 μM). During control condition the hearts exhibit CA between 50 and 90 cm H 2 O; with basal coronary flow at 60 cm H 2 O of 5.18+0.21 ml/min. Basal NO 2. , TBARS and O 2. release were 0.61+0.14 nmol/min/g wt, 0.78+0.05 μmol/min/g wt and 14.44+1.93 nmol/min/g wt, respectively. Dipyridamole induced significant vasodilatation below autoregulatory range (20 % at 40 cm H 2 O), but not during and above autoregulatory range (about 10% at all CPP values). Furthermore, dipyridamole-induced changes of CF was accompanied with significant increase of NO 2. at all values of CPP (from 386% at 40 cm H 2 O to 174% at 120 cm H 2 O), and significant increase of O 2. at all values of CPP (from 161% at 40 to 52% at 120 cm H 2 O), but not significant changes in TBARS release. However, perfusion with L-NAME completely reversed the effects of dipyridamole -induced inhibition. Dipyridamole -induced dilation was increased under L-NAME (from 22% at 40 cm H 2 O to 34% at 120 cm H 2 O) without changes in autoregulatory range. NO 2. was significantly increased under L-NAME (from 204% at 40 cm H 2 O to 123% at 120 cm H 2 O), what was also case with TBARS release (from 28% at 80 cm H 2 O to 194% at 120 cm H 2 O) and O 2. release (from 86% at 40 cm H 2 O to 69% at 120 cm H 2 O). Our findings clearly show that dipyridamole might affect coronary flow, NO 2. , TBARS and O 2. release in isolated rat heart.