PHOSPHODIESTERASE ISOFORMS IN THE PULMONARY ARTERIAL CIRCULATION OF THE RAT - CHANGES IN PULMONARY-HYPERTENSION

Phosphodiesterase (PDE) activity was determined in pulmonary arteries removed from control and chronic hypoxia-induced pulmonary hypertensiv e rats. The main, first-branch, intrapulmonary and resistance pulmonar y arteries were studied. We measured total cAMP PDE activity and cGMP PDE activity, as well as that of individual isoforms (PDE1-5). cAMP PD E activity in chronic hypoxic rats was increased in first-branch and i ntrapulmonary arteries from hypoxic rats. No changes were observed in the main or resistance pulmonary arteries. Similarly, cGMP PDE activit y was increased in the main, first-branch and intra-pulmonary arteries of the hypoxic rats. No changes in cGMP PDE activity were observed in resistance arteries. There was evidence for PDE1-5 activity in all pu lmonary arteries. The increased cAMP PDE activity in first-branch and intrapulmonary vessels was associated with an increase in cilostimide- inhibited PDE (PDE3) activity. increased total cGMP PDE in main pulmon ary artery was associated with increases in Ca++/calmodulin-stimulated (PDE1) activity. An increase in zaprinast-inhibited (PDE5) activity w as observed in first-branch and intrapulmonary arteries. Our results s uggest that decreases in intracellular cyclic nucleotide levels in pul monary arteries from pulmonary hypertensive rats are associated with i ncreased PDE activity. Further, these changes may reflect alterations at the level of specific types of PDE isoforms.