Tumor necrosis factor (TNF)-α transgenic mice have previously been found to have characteristics consistent with emphysema and severe pulmonary hypertension. Lungs demonstrated alveolar enlargement as well as interstitial thickening due to chronic inflammation and perivascular fibrosis. In the present report, we sought to determine potential mechanisms leading to development of pulmonary hypertension in TNF-α transgenic mice. To determine if sustained vasoconstriction was an important component of this pulmonary hypertension, nitric oxide was administered and hemodynamics measured. 25 ppm NO failed to normalize right ventricular pressure in transgene positive mice suggesting that the pulmonary hypertension was not due to sustained vasoconstriction. Structural analysis of the pulmonary arteries found adventitial thickening and a trend toward medial hypertrophy in pulmonary arteries of transgene positive mice suggesting that vascular remodeling had occurred. Echocardiographic measurement of the percent fractional shortening of the left ventricle as a measurement of ventricular function in vivo revealed left ventricular dysfunction was not contributing to pulmonary hypertension. We examined expression of genes known to be important in regulation of vascular tone and structure. Messenger RN
To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.