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 arte rial pressure (MAP), mean circulatory filling pressure (MCFP), total p eripheral resistance (TPR), cardiac output (GO) and resistance to veno us return (RV) were studied in rats. 2 In pentobarbitone-anaesthetized rats given mecamylamine (ganglionic blocker, 3.7 mu g kg(-1)) and nor adrenaline (1.5 mu g kg(-1) min(-1)) to suppress autonomic reflexes, p inacidil (60 and 180 mu g kg(-1) min(-1)), relative to the vehicle, re duced 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)) cau sed 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 sign ificantly alter MCFP. 4 Our results show that pinacidil is an efficaci ous vasodilator of arterial resistance blood vessels but has little ve nodilator activity.