Angiotensin II infusion restores stimulated angiogenesis in the skeletal muscle of rats on a high-salt diet.
Elevated dietary salt intake has previously been demonstrated to have dramatic effects on microvascular structure and function. The purpose of this study was to determine whether a high-salt diet modulates physiological angiogenesis in skeletal muscle. Male Sprague-Dawley rats were placed on a control diet (0.4% NaCl by weight) or a high-salt diet (4.0% NaCl) before implantation of a chronic electrical stimulator. After seven consecutive days of unilateral hindlimb muscle stimulation, animals on control diets demonstrated a significant increase in microvessel density in the tibialis anterior muscle of the stimulated hindlimb relative to the contralateral control leg. High salt-fed rats demonstrated a complete inhibition of this angiogenic response, as well as a significant reduction in plasma ANG II levels compared with those of control animals. To investigate the role of ANG II suppression on the inhibitory effect of high-salt diets, a group of rats that were fed high salt were chronically infused with ANG II at a low dose. Maintenance of ANG II levels restored stimulated angiogenesis to control levels in animals fed a high-salt diet. Western blot analysis indicated that inhibition of angiogenesis in high salt-fed rats was not due to changes in VEGF or VEGF receptor type 1 protein expression in response to stimulation; however, the degree to which VEGF receptor 2 protein increased with stimulation was significantly lower in high salt-fed animals. This study demonstrates an inhibitory effect of high salt intake on stimulated angiogenesis and suggests a critical role for ANG II suppression in mediating this antiangiogenic effect.
Petersen
Matthew C
MC
Deparment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Munzenmaier
Diane H
DH
Greene
Andrew S
AS
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000804:Angiotensin II / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II