Cyclic nucleotide phosphodiesterase in heart and aorta of spontaneously hypertensive rats

Abstract

Cyclic AMP and cyclic GMP phosphodiesterase (3′:5′-cyclic-AMP 5′-nucleotidohydrolase, EC 3.1.4.17) activities were compared in soluble ( 105 000 × g supernatant ) and particulate ( 105 000 × g pellet of 700 × g supernatant ) fractions of heart and aorta of hypertensive and normotensive rats at 5 μM and 100 μM substrate concentrations. Cyclic AMP phosphodiesterase activity was significantly higher ( P < 0.05) in particular fractions of hypertensive rat aorta at 100 μM, while no significant changes were observed in heart. Cyclic GMP phosphodiesterase activity was significantly increased ( P < 0.05) in particulate and soluble fractions of hypertensive rat heart compared to normotensive rat at both substrate concentrations, but there were no differences in aorta. When phosphodiesterase activities in the soluble fractions of aorta and heart were examined as a function of enzyme concentration, rectilinear rates were observed with micromolar, but not with millimolar concentrations of cyclic AMP or cyclic GMP. Double reciprocal plots for cyclic AMP phosphodiesterase activity were non-linear in heart and aorta supernatants. Similarly, cyclic GMP phosphodiesterase yielded non-linear kinetics in heart supernatant, however, the plots were linear for aorta supernatant. Particulate fractions of heart showed linear kinetics for cyclic AMP and cyclic GMP phosphodiesterase and the K m values were in the range of high K m for soluble enzymes. V in hypertensive rats was approximately doubled compared to normotensive rats for cyclic AMP and cyclic GMP phosphodiesterase. These data suggest that altered phosphodiesterase activity could result in a change in cyclic nucleotide index in the cardiovascular tissues of hypertensive rat.