Angiotensin II is a critical mediator of prazosin-induced angiogenesis in skeletal muscle.
OBJECTIVE
The purpose of this study was to determine whether a high-salt diet modulates physiological angiogenesis in skeletal muscle by altering angiotensin 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 ANGII suppression by high salt, and a group of rats fed control diet were treated with the angiotensin II type I (AT(1)) receptor blocker losartan and prazosin.


RESULTS
Prazosin induced significant angiogenesis in the tibialis anterior muscle after 1 week of treatment. High-salt-fed rats demonstrated a complete inhibition of this angiogenic response. Maintenance of ANGII levels restored prazosin-induced angiogenesis in animals fed a high-salt diet. In addition, losartan treatment blocked prazosin-induced angiogenesis in animals on a control diet. Western blot analysis indicated that prazosin-induced angiogenesis was independent 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 a critical pathway in this model of angiogenesis.
Petersen
Matthew C
MC
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Greene
Andrew S
AS
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D044140:Receptor, Angiotensin, Type 1; D042461:Vascular Endothelial Growth Factor A; D014665:Vasodilator Agents; D000804:Angiotensin II; D012965:Sodium Chloride; D019808:Losartan; D011224:Prazosin
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