EFFECTS OF PINACIDIL ON ARTERIAL AND VENOUS RESISTANCES AND MEAN CIRCULATORY FILLING PRESSURE IN RATS

1 The effects of the potassium channel opener, pinacidil, on mean arterial pressure (MAP), mean circulatory filling pressure (MCFP), total peripheral resistance (TPR), cardiac output (GO) and resistance to venous return (RV) were studied in rats. 2 In pentobarbitone-anaesthetized rats given mecamylamine (ganglionic blocker, 3.7 mu g kg(-1)) and noradrenaline (1.5 mu g kg(-1) min(-1)) to suppress autonomic reflexes, pinacidil (60 and 180 mu g kg(-1) min(-1)), relative to the vehicle, reduced MAP and TPR in a dose-dependent manner but did not significantly alter CO, MCFP or R(nu). 3 Pinacidil (10-300 mu g kg(-1) min(-1)) caused similar increases in MCFP, an inverse index of venous compliance, and similar dose-dependent reductions in mean arterial pressure (MAP) in conscious, intact rats and rats infused with the ganglionic blocker, hexamethonium (150 mu g kg(-1) min(-1)). In rats with vasomotor tone elevated by the infusion of noradrenaline (1.5 mu g kg(-1) min(-1)), pinacidil caused markedly greater depressor responses but did not significantly alter MCFP. 4 Our results show that pinacidil is an efficacious vasodilator of arterial resistance blood vessels but has little venodilator activity.