ZAPRINAST INCREASES CYCLIC-GMP LEVELS IN PLASMA AND IN AORTIC TISSUE OF RATS

The purpose of this study was to determine if significant relationship s exist between plasma and aortic cyclic GMP (cGMP) levels and pharmac odynamic effect after the i.v. administration of the cGMP-selective ph osphodiesterase inhibitor zaprinast to conscious, spontaneously hypert ensive rats. Zaprinast dose-dependently increased plasma and aortic cG MP levels at 10, 18 and 30 mg/kg and decreased mean arterial blood pre ssure (MAP) at 18 and 30 mg/kg. The concentrations of cGMP in the plas ma and in the aorta were significantly correlated (r=0.765, P<0.0001). The changes in MAP were significantly correlated to aortic (r=-0.750, P<0.0001) and plasma (r=-0.762, P<0.0001) cGMP levels. We conclude th at plasma cGMP may be an index of cGMP-selective phosphodiesterase inh ibition in vivo.