Tumor necrosis factor-alpha induces vascular hyporesponsiveness in Sprague-Dawley rats

The cytokine tumor necrosis factor-alpha (TNF alpha) is one of the major mediators of septic shock. Because vasodilation is a hallmark of sepsis and decreased vascular responsiveness has been implicated in the pathogenesis of septic shock, we studied the effect of TNF alpha on the mean blood pressure in conscious rats and vascular responsiveness to vasoconstrictors ex vivo using the standard organ bath method. Intravenous infusion of TNF alpha (0.006 or 0.06 mg/kg/hr for 10 hours) decreased mean blood pressure in a dose-dependent fashion. Contractile responses to norepinephrine were depressed dose-dependently in the aortic rings both with and without its endothelium. Aortic contractions by potassium depolarization were also depressed. These results suggest that TNF alpha induces non-specific vascular hyporesponsiveness, which is independent of the presence of the endothelium. The TNF alpha-induced vascular hyporesponsiveness might contribute to the hypotensive action of TNF alpha.