Angiotensin II is a critical mediator of prazosin-induced angiogenesis in skeletal muscle

Objective: The porpose of this study waas to determine whether a high-salt diet modulates physiological angiogenesis in skeletal muscle by altering angiotension II (ANGII) and vascular endothelial growth factor (VEGF) levels. Methods: Sprague-Dawley rats were placed on a control diet (0.4% NaCl by weight) or high-salt diet (4.0% NaCl) prior to treatment with the vasodilator prazosin in the drinking water. In addition, a group of animals fed high-salt were infused intravenously with ANGII at a low dose to prevent ANGLL supression by high salt, and a group of rats fed control diet were treated with the angiotensis II type I (AT(1)) receptor blocker lasortan and prazosin. Results: Prazosin induced significant angiogenesis in the tibialis anterior muscle after 1 week of treatment. High-salt-fed rats demonstarted a complete inhibition of this angiogenic response. Maintenance of ANGII levels resorted prazosin-induced angiogenesis was independant of changes in muscle levels of VEGF. Conclusions: This study demonstrates an inhibitory effect of high salt intake on prazosin-induced angiogenesis. Further, these results indicate that ANGII acting through the AT(1) receptor is critical pathway in this model of angiogenesis.