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Presented at High Frequency Ventilation Conference, Snowbird Utah, April 4-9, 2000
Inhibition of cGMP Phosphodiesterase (PDE-5) with UK114542 Reduces Pulmonary Hypertension in Hypoxic Lambs. Ling CY, Dahl MJ, Kaur A, et al. University of Utah, Salt Lake City, UT.
Nitric oxide reduces pulmonary hypertension by activating soluble guanylate cyclase, which converts GTP to cGMP in vascular smooth muscle. UK114542 is a new potent inhibitor of PDE-5. This drug decreases the hydrolysis of cGMP thus enhancing pulmonary vasodilation. The effects of this compound were studied in 3 week old lambs with hypoxia-induced pulmonary hypertension. UK114542 caused a 27% decrease in PVR that lasted for at least 90 minutes. This was similar to the 32% decrease on PVR observed with 1 hr of iNO. SVR also decreased transiently during iv infusion of UK114542 , but not during exposure to iNO. The authors speculate that this PDE-5 inhibitor might be useful to treat PPHN in infants who do not respond to iNO.