[Role of endothelial-derived nitric oxide and its synthase in the development of hypoxic pulmonary hypertension in rat].

To clarify the role of endothelial-derived nitric oxide (EDNO) and its synthase (NOS) in the normal and hypertensive pulmonary vasculature, activity of endothelial NOS in the lungs, ENDO-dependent vasodilating response induced by bradykinin (BK), and cGMP content of lung tissue in normoxic and hypoxic rats were investigated. We also studied the effects of NOS inhibitor-L-NAME on the activity of NOS, cGMP content, mean pulmonary arterial pressure (mPAP) and carotid systolic arterial pressure (CAPs) in both rats. The results were as follows (1) In normoxic rats there was no NOS activity in the endothelium of small vessels (phi < or = 80 microns) and no relaxing response to BK. Long-term administration of L-NAME obviously inhibited the activity of ecNOS and cGMP content in the lungs of normoxic rats, therefore it led to the increment of CAPs but failed to elevate mPAP. (2) After hypoxic exposure for 10 days, NADPH-diaphorase (NADPH-d and ecNOS immunoreactivity turned to be positive in the endothelium of small vessels with diameter less than 80 microns. BK-induced EDNO-dependent vasodilation, the enzyme activity of cNOS and cGMP content in the lungs of hypoxic rats were significantly enhanced as compared with normoxic rats. Long-term administration of L-NAME in hypoxic rats markedly inhibited the enhancement of cNOS enzyme activity, the production of EDNO and cGMP content in rat lungs, consequently it significantly decreased mPAP but elevated CAPs obviously. These results suggest that the role of EDNO in maintaining the low basal tone of normal adult pulmonary circulation remain to be studied more precisely. The increased activity of ecNOS and the enhancement of EDNO synthesis might act to moderate the hypertension. The excess synthesis of EDNO might be toxic to the endothelium of pulmonary vessels, therefore potentiating the development of pulmonary hypertension.