Zaprinast, a type V phosphodiesterase inhibitor, dilates capacitance vessels in anaesthetised rats.
The effects of zaprinast (a type V phosphodiesterase inhibitor) on mean arterial pressure, heart rate, cardiac output, mean circulatory filling pressure, arterial and venous resistances were compared to those of sodium nitroprusside in three groups, each of intact or ganglion-blocked, Inactin-anaesthetised rats. In intact rats, zaprinast (1.5, 3.0 mg kg(-1) min(-1)) and sodium nitroprusside (8.0, 64.0,microg kg(-1) min(-1)) dose-dependently reduced mean arterial pressure and arterial resistance, but did not alter cardiac output and venous resistance. Both increased heart rate, with the effect of zaprinast less than that of sodium nitroprusside. Mean circulatory filling pressure was elevated by both doses of zaprinast but only the high dose of sodium nitroprusside. In rats given mecamylamine (3.7 micromol kg(-1), i.v. bolus) and noradrenaline (7.3 nmol kg(-l) min(-1)), zaprinast and sodium nitroprusside elicited dose-dependent reductions in mean arterial pressure, arterial and venous resistances, and mean circulatory filling pressure. Both increased cardiac output, with the effect of zaprinast greater than that 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 capacitance vessels in ganglion-blocked rats infused with noradrenaline to restore vasomotor tone. Zaprinast but not sodium nitroprusside has a direct, negative chronotropic effect on the heart.
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of British Columbia, Vancouver, Canada.
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D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005730:Ganglionic Blockers / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011688:Purinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018924:Vascular Capacitance / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects / Q000502:physiology
D005730:Ganglionic Blockers; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D008464:Mecamylamine; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517384:Pde5a protein, rat; C011145:zaprinast; D009638:Norepinephrine