Existence of a local renin angiotensin system in the skeletal muscle microcirculation

The renin angiotensin system (RAS) has classically been considered an endocrine system. More recently, local renin angiotensin systems have been found in various organs and tissues throughout the body. These local renin angiotensin systems have the components made by the cells of the tissue or organ and produce angiotensin II (ANGII) without the need for these substances or enzymes to be transported by the circulation.; In the first part of this study, the components and product of the RAS were found to be present in the skeletal muscle microvasculature. The presence of renin and angiotensinogen (ATGN) was shown by immunohistochemical analysis of the cremaster muscle. The presence of the product of the RAS, ANGII, was also shown to be present in isolated microvessels by HPLC separation and measurement by radioimmunoassay. The concentration of the ANGII in the microvessels was consistently found to be higher than the concentration of ANGII in the plasma of the same animals.; The second part of these studies focused on the source of the renin and ANGII found within the skeletal muscle microvessels. We performed a set of experiments where the rats were bilaterally nephrectomized to remove the renal source of renin. The nephrectomized animals demonstrated that the microvascular RAS did not depend on renal renin because ANGII concentrations did not decrease in nephrectomized animals.; The third part of these studies analyzed the regulation of the local microvessel RAS by salt, ACE inhibition, and electrical stimulation. Amount of dietary sodium intake, a strong regulator of the endocrine RAS, was shown to have no effect on the local microvessel RAS. A strong regulator of the total muscle ANGII concentration was electrical stimulation of rat hind-limb muscles. The muscle stimulation led to an increase in the local ANGII concentration measured in homogenized tibialis anterior muscle. The same stimulus caused no change in the plasma ANGII concentration. The differences found between the regulation of the local microvessel RAS and the endocrine RAS suggest that these two systems play different physiologic roles within the body.