FACTORS INFLUENCING THE IDIOPATHIC DEVELOPMENT OF PULMONARY-HYPERTENSION IN THE FAWN HOODED RAT

Fawn hooded rats (FHR), a strain of rat with a hereditary bleeding tendency due to a genetic defect in platelet aggregation, have recently been found to develop pulmonary hypertension. However, whether the pulmonary hypertension in FHR has a genetic basis or simply reflects the influence of extrinsic factors known to increase pulmonary artery pressure in other rat strains has not been fully evaluated. To further examine the structural and hemodynamic changes of pulmonary hypertension in FHR, and to investigate the extent to which alveolar hypoxia may have promoted these abnormalities, hemodynamic and morphometric measurements were made in FHR (4 to 24 wk) and compared with age-matched Sprague-Dawley (SDR) control rats. Increases in mean pulmonary artery pressure, total pulmonary resistance, and right ventricular enlargement were present in both male and female FHR and were evident at an early age (4 wk). Morphometric analysis of barium gelatin-infused lungs revealed marked pulmonary vascular remodelling in FHR characterized as extension of muscle into more peripheral pulmonary vessels, medial hypertrophy of proximal vessels, and reduced number of barium-filled arteries. The increases in pulmonary artery pressure in FHR were not due to the influence of more severe hypoxia, hypoventilation, or polycythemia, as blood gas tension and hematocrit were similar in FHR and SDR. Moreover, we found that pulmonary hypertension could be transmitted to backcross and second filial generation offspring arising from selective matings between FHR and control Wistar Kyoto rats, confirming the heritable basis for pulmonary hypertension in the FHR. However, the ability to suppress the appearance of pulmonary hypertension in FHR by continuous exposure to a mildly oxygen-enriched environment suggests that environmental stimuli can influence the expression of the genetic predisposition in this rat strain.