A Ca channel blocker, benidipine, increases coronary blood flow and attenuates the severity of myocardial ischemia via NO-dependent mechanisms in dogs

Objectives. This study was undertaken to examine whether a dihydropyridine Ca channel blocker, benidipine, increases cardiac NO levels, and thus coron ary blood flow (CBF) in ischemic hearts. Background. Benidipine protects endothelial cells against ischemia and repe rfusion injury in hearts. Methods and Results. In open chest dogs, coronary perfusion pressure (CPP) of the left anterior descending coronary artery was reduced so that CBF dec reased to one-third of the control CBF, and thereafter CPP was maintained c onstant (103 +/- 8 to 42 +/- 1 mmHg). Both fractional shortening (FS: 6.1 /- 1.0%) and lactate extraction ratio (LER: -41 +/- 4%) decreased. Ten minu tes after the onset of an intracoronary infusion of benidipine (100 ng/kg/m in), CBF increased from 32 +/- 1 to 48 +/- 4 ml/100g/min during 20 min with out changing CPP (42 +/- 2 mmHg), Both FS (10.7 +/- 1.2%) and LER (-16 +/- 4%) also increased. Benidipine increased cardiac NO levels (11 +/- 2 to 17 +/- 3 nmol/ml), The increases in CBF, FS, LER and cardiac NO levels due to benidipine were blunted by L-NAME. Benidipine increased cyclic GMP contents of the coronary artery of ischemic myocardium (139 +/- 13 to 208 +/- 15 fm ol/mg protein), which was blunted by L-NAME. Conclusion. Thus, we conclude that benidipine mediates coronary vasodilatio n and improves myocardial ischemia through NO-cyclic GMP dependent mechanis ms. (C) 1998 by the American College of Cardiology.