ZAPRINAST, A TYPE-V PHOSPHODIESTERASE INHIBITOR, DILATES CAPACITANCE VESSELS IN ANESTHETIZED RATS

The effects of zaprinast (a type V phosphodiesterase inhibitor) on mea n arterial pressure, heart rate, cardiac output, mean circulatory fill ing pressure, arterial and venous resistances were compared to those o f sodium nitroprusside in three groups, each of intact or ganglion-blo cked, Inactin-anaesthetised rats. In intact rats, zaprinast (1.5, 3.0 mg kg(-1) min(-1)) and sodium nitroprusside (8.0, 64.0 mu g kg(-1) min (-1)) dose-dependently reduced mean arterial pressure and arterial res istance, but did not alter cardiac output and venous resistance. Both increased heart rate, with the effect of zaprinast less than that of s odium nitroprusside. Mean circulatory filling pressure was elevated by both doses of zaprinast but only the high dose of sodium nitroprussid e. In rats given mecamylamine (3.7 mu mol kg(-1), i.v. bolus) and nora drenaline (7.3 nmol kg(-1) min(-1)), zaprinast and sodium nitroprussid e elicited dose-dependent reductions in mean arterial pressure, arteri al and venous resistances, and mean circulatory filling pressure. Both increased cardiac output, with the effect of zaprinast greater than t hat of sodium nitroprusside at the low dose. Zaprinast but not sodium nitroprusside reduced heart rate. Our results indicate that zaprinast, similar to sodium nitroprusside, dilates both resistance and capacita nce vessels in ganglion-blocked rats infused with noradrenaline to res tore vasomotor tone. Zaprinast but not sodium nitroprusside has a dire ct, negative chronotropic effect on the heart. (C) 1998 Elsevier Scien ce B.V. All rights reserved.