TNF alpha is required for hypoxia-mediated right ventricular hypertrophy

Hypoxia has been shown to activate the pleiotropic cytokine TNF alpha in the lung. TNF alpha in turn, is known to induce pulmonary vasoconstriction. Additional effects of this cytokine in hypoxia mediated cardiopulmonary remodeling are poorly understood. To further evaluate the role of TNF alpha in chronic hypoxia we exposed TNF alpha null (TNF alpha-/-) and wild-type mice to three weeks of hypobaric hypoxia (10% O-2). Equivalent erythocytosis (Hematocrit increased by greater than or equal to 40%) developed in both genetic backgrounds. In contrast, right ventricular systolic pressure increased in response to three weeks of hypoxia in the wild-type mice (greater than or equal to 75%), yet was unaltered in the TNF alpha-/- mice. Concomitantly right ventricular hypertrophy was attenuated in the TNF alpha-/- mice (35 +/- 5% increase) when compared to wild-type mice (124 +/- 6% increase p < 0.001, n greater than or equal to 20). Interestingly in both strains the lung wet weights increased to a similar degree in response to hypoxia. In conclusion, our data demonstrate that TNF alpha is an integral autocoid in chronic hypoxia mediated right ventricular hypertrophy. Moreover, additional components of cardiopulmonary remodeling may be regulated by TNF alpha signaling as suggested by the negligible right ventricular systolic pressure response to hypoxia in the absence of TNF alpha.