title: Role of local and systemic angiotensin in diabetic renal disease.
abstract: Classically, the renin-angiotensin system (RAS) in diabetes was thought to be suppressed, and relatively unimportant in the regulation of hemodynamics and the development of complications. However, studies of pharmacologic interruption of the RAS with angiotensin converting enzyme (ACE) inhibition have implicated the RAS in the progression of diabetic nephropathy. Preliminary evidence also suggests a beneficial effect of angiotensin II receptor antagonists. The relative roles of the systemic versus intrarenal RAS in this process are under active investigation. Though plasma renin is generally low, there may be subtle changes in angiotensin (Ang) II metabolism that sustain relatively higher plasma Ang II levels. Furthermore, the intrarenal RAS may not be suppressed. Renal renin levels tend to be disproportionately elevated, as compared to plasma values. Renal Ang II levels are normal, and renal mRNAs for RAS components have been variable. In general, lack of intrarenal RAS suppression (despite plasma volume and increased exchangeable sodium) may indicate inappropriate activity of the local tissue RAS, and act as a proximate cause of the systemic RAS suppression. Ang II-mediated injury may occur via stimulation of sclerosing mediators, and there is evidence that hyperglycemia acts synergistically with Ang II to promote cellular injury. Together, these recent investigations lend further support to the notion that the RAS plays an important role in diabetic nephropathy, and are helping to shed light on the mechanisms of progressive renal injury.
authors.affiliation: Department of Medicine, Oregon Health Sciences University, Portland, USA. anderssh@ohsu.edu
authors.forename: S
authors.initials: S
authors.lastname: Anderson
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D012084:Renin-Angiotensin System / Q000502:physiology
chemical_list: D000804:Angiotensin II