Abstract

Angiotensin (ANG) II plays a vital role in blood pressure regulation and body fluid homeostasis. Although many peripheral tissues synthesize components of the renin-ANG system, very few synthesize all of the major components involved in the generation ofANG II. This study used interscapular brown adipose tissue (ISBAT) as a model system to evaluate the mechanism of ANG II generation in an extrarenal tissue. Polymerase chain reaction analysis of DNA from ISBAT demonstrated angiotensinogen gene expression; however, renin gene expression was not detected. Renin activity that was not completely derived from the residual blood pool was detected in ISBAT homogenates. Kinetic parameters for renin activity were similar in ISBAT and adrenal gland. Renin activity was partially inhibited by anti-renin antibody and completely inhibited by a specific rat renin inhibitor. Bilateral nephrectomy did not decrease renin activity in ISBAT. Western blot analysis, employing two species-specific renin antibodies, indicated the presence of a variety of isoforms of renin in ISBAT. The presence of renin activity in isolated brown adipocytes demonstrated that the enzyme is localized to adipocytes. The release of immunoreactive ANG peptides from ISBAT slices over 3 h indicated de novo synthesis. These studies support the existence of a local renin-ANG system in ISBAT and suggest involvement of renin in the formation of ANG II.

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