Physiologic actions and molecular expression of the renin-angiotensin system in the diabetic rat

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Abstract

Clinical, experimental, biochemical, and molecular biologic studies all invoke an important role for the renin-angiotensin system (RAS) in the pathogenesis of diabetic complications. Studies of pharmacologic interruption of the RAS with angiotensin-converting enzyme (ACE) inhibition have implicated this hormonal system in the progression of diabetic nephropathy, both experimentally and clinically. Preliminary evidence also suggests a beneficial effect of angiotensin II (Ang II) receptor antagonists. The relative roles of the systemic vs. intrarenal RAS in the pathogenesis of diabetic nephropathy have recently been evaluated. Though plasma renin is generally low, it is not yet clear whether RAS component processing is normal in diabetes; there may be subtle changes in Ang II metabolism which 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 renin values. Renal Ang II levels are normal, and renal mRNAs for RAS components have been variable, though not suppressed. In general, lack of RAS suppression (despite plasma volume and increased exchangeable sodium) may indicate inappropriate activity of the RAS in diabetes. Indeed, disproportionate activity of the intrarenal RAS may be a proximate cause of the observed suppression of the systemic RAS. RAS-mediated injury may occur via stimulation of a number of sclerosing mediators, and there is evidence that hyperglycemia acts synergistically with Ang II to promote cellular injury. Together, these recent investigations lend support to the notion that the RAS plays an important role in diabetic nephropathy, and are beginning to shed light on the mechanisms of progressive renal injury.

Original languageEnglish (US)
Pages (from-to)406-411
Number of pages6
JournalMineral and Electrolyte Metabolism
Volume24
Issue number6
DOIs
StatePublished - Nov 1 1998

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Keywords

  • Albuminuria
  • Angiotensin
  • Angiotensin-converting enzyme
  • Diabetes
  • Renin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry

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