Increased bradykinin and 'normal' angiotensin peptide levels in diabetic Sprague-Dawley and transgenic (mRen-2)27 rats

D. J. Campbell, D. J. Kelly, J. L. Wilkinson-Berka, M. E. Cooper, S. L. Skinner

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Abstract

Background. The transgenic (mRen-2)27 rat (TGR) is a high tissue renin, high angiotensin (Ang) II model of hypertension. When administered streptozotocin (STZ), TGRs develop a rapidly progressive diabetic nephropathy with renal failure over 12 weeks. Bradykinin (BK) and Ang II are potent vasoactive peptides that may participate in the vascular and metabolic abnormalities of diabetes. Methods. TGR and Sprague-Dawley (SD) rats were administered STZ (diabetic) or citrate buffer (nondiabetic) at six weeks of age. Diabetic rats received daily ultralente insulin to maintain moderate hyperglycemia (~18 mM). Rats were sacrificed four- and eight-weeks post-STZ or vehicle. Results. Diabetes did not modify the blood pressure of either SD rats or TGRs. Diabetes increased levels of BK-(1-9) and its metabolite BK- (1-7) in kidney, aorta, and heart of both SD rats and TGRs. Diabetes did not influence Ang II levels in plasma, kidney, aorta, heart, or adrenal gland of SD rats, but reduced to normal the elevated Ang II levels in plasma, kidney, aorta, and adrenal gland of TGRs. Conclusions. STZ-induced diabetes was associated with elevated tissue levels of BK-(1-9) and 'normal' circulating and tissue levels of Ang II. The increased BK-(1-9) levels were consistent with the participation of this peptide in the vascular and metabolic abnormalities of diabetes. However, the rapidly progressive nephropathy of diabetic TGRs was not associated with BK-(1-9) and Ang II levels in target organs that differed from those of diabetic SD rats.

Original languageEnglish
Pages (from-to)211-221
Number of pages11
JournalKidney International
Volume56
Issue number1
DOIs
Publication statusPublished - 1999
Externally publishedYes

Keywords

  • Angiotensin converting enzyme
  • Diabetic nephropathy
  • Endopeptidase
  • Hypertension
  • Prorenin

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