Angiotensin II-induced increases in mean arterial pressure (151 vs 123 mm Hg), salt intake, and cardiac hypertrophy were significantly attenuated in TNF-alpha knockout mice compared to wild-type.
Does TNF-alpha knockout prevent Angiotensin II-induced salt appetite, hypertension, and cardiac hypertrophy in mice?
TNF-alpha plays a mechanistic role in mediating chronic Angiotensin II-induced effects on salt appetite, blood pressure, and cardiac hypertrophy in mice.
Hypertension is considered a low-grade inflammatory condition induced by various proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha. Recent studies have implicated an involvement of TNF-alpha in the development of salt-sensitive hypertension induced by angiotensin II (Ang II). To understand further the relationship between TNF-alpha and Ang II, we examined the responses to Ang II in TNF-alpha knockout (TNF-alpha(-/-)) mice in the present study. A continuous infusion of Ang II (1 microg/kg per minute) for 2 weeks was given to both TNF-alpha(-/-) and wild-type (WT) mice with implanted osmotic minipumps. Daily measurement of water intake, salt intake, and urine output were performed using metabolic cages. Blood pressure was monitored continuously with implanted radiotelemetry. Ang II administration for 2 weeks caused increases in salt (0.2+/-0.07 to 5.6+/-0.95 mL/d) and water (5.4+/-0.34 to 11.5+/-1.2 mL/d) intake and in mean arterial pressure (115+/-1 to 151+/-3 mm Hg) in wild-type mice, but these responses were absent in TNF-alpha(-/-) mice (0.2+/-0.04 to 0.3+/-0.09 mL/d, 5.5+/-0.2 to 6.1+/-0.07 mL/d, and 113+/-2 to 123+/-3 mm Hg, respectively). Cardiac hypertrophy induced by Ang II was significantly attenuated in TNF-alpha(-/-) mice compared with wild-type mice. In a group of TNF-alpha(-/-) mice, when replacement therapy was made with recombinant TNF-alpha, Ang II induced similar responses in salt appetite, mean arterial pressure, and cardiac hypertrophy, as observed in wild-type mice. These results suggest that TNF-alpha plays a mechanistic role in mediating chronic Ang II-induced effects on salt appetite and blood pressure, as well as on cardiac hypertrophy.
Sriramula et al. (2008) studied Hypertension. Angiotensin II vs. Wild-type mice was evaluated on Salt intake, water intake, and mean arterial pressure. Angiotensin II-induced increases in mean arterial pressure (151 vs 123 mm Hg), salt intake, and cardiac hypertrophy were significantly attenuated in TNF-alpha knockout mice compared to wild-type.