Mild hypoxia causes severe pulmonary hypertension in fawn-hooded but not in Tester Moriyama rats

The purpose of this study was to test whether the Tester Moriyama rat (TMR) , a strain that has a serotonin platelet storage-pool deficiency similar to that of the fawn-hooded rat (FHR), develops severe pulmonary hypertension (PH) upon exposure to mild hypoxia. We compared hemodynamic parameters in c atheterized 10-week-old FHR, TMR, and control Wistar rats that had been rai sed from birth to 10 weeks of age under normoxia (PIO2 similar to 150 mmHg) or mild hypobaric hypoxia (PIO2 similar to 120 mmHg). Mean pulmonary arter y pressure and right ventricle to left ventricle plus septum weight ratio w ere much higher in the mildly hypoxic FHR compared with the normoxic FHR. T hese parameters were only increased slightly by exposure to mild hypoxia in the TMR and Wistar rats. Mild hypoxia did not affect mean systemic artery pressure in any of the rat strains, Exposure of FHR to mild hypoxia from 4 to 10 weeks of age did not lead to development of PH. Endothelin-1 (ET-1) m RNA and peptide levels were increased in the hypertensive lungs of mildly h ypoxic FHR compared with the normotensive lungs of normoxic FHR, and of nor moxic and mildly hypoxic TMR and Wistar rats. These results suggest that mi ld hypoxia causes severe PH and upregulation of lung ET-1 expression in neo natal FHR but not in neonatal TMR, and that the period from birth to 4 week s of age is critical for the development of the severe PH in the FHR. A ser otonin PSPD does not predispose rats to hypoxia-induced PH. (C) 2001 Elsevi er Science B.V. All rights reserved.