Faculty Collaboration Database

Early diabetes mellitus stimulates proximal tubule renin mRNA expression in the rat. Kidney Int 2000 Dec;58(6):2320-30

Date

12/15/2000

Pubmed ID

11115066

DOI

10.1046/j.1523-1755.2000.00416.x

Scopus ID

2-s2.0-0033672308 (requires institutional sign-in at Scopus site)   122 Citations

Abstract

BACKGROUND: Enhanced intrarenal angiotensin II (Ang II) activity may contribute to diabetic nephropathy. The proximal tubule is a proposed site of significant intrarenal Ang II production. We determined the effect of early diabetes on mRNA expression of components of the proximal tubule renin-angiotensin system.

METHODS: Three groups of male Sprague-Dawley rats were studied after two weeks: (1) control (C), (2) streptozotocin-induced diabetes (STZ), and (3) STZ-induced diabetes, with normoglycemia maintained by insulin implants (STZ-I). Competitive reverse transcription-polymerase chain reaction was used to assay mRNA for renin, angiotensinogen, and angiotensin-converting enzyme in suspensions of proximal tubules; plasma and kidney levels of Ang II were measured by radioimmunoassay, and Western analysis of Ang II subtype 1 (AT1) receptors was performed.

RESULTS: STZ rats tended to have increased plasma and intrarenal levels of Ang II compared with C and STZ-I rats. In proximal tubules, mRNA for renin was significantly increased in STZ rats, with reversal to control values in STZ-I rats (C, 2432 +/- 437 vs. STZ, 5688 +/- 890 fg/0.25 microg RNA, P < 0.05 vs. C, N = 9, vs. STZ-I, 1676 +/- 376 fg/0.25 microg RNA, P = NS vs. C). In STZ rats, the AT1 receptor antagonist losartan caused a further fivefold increase in proximal tubule renin mRNA, associated with proximal tubular renin immunostaining. STZ had no significant effect on mRNA expression for angiotensinogen or angiotensin-converting enzyme in proximal tubules. By Western blot analysis, cortical and proximal tubule AT1 receptor protein expression was significantly decreased in STZ rats.

CONCLUSIONS: These data suggest activation of the proximal tubule renin-angiotensin system in early STZ diabetes, mediated at least partly by enhanced expression of renin mRNA. Increased local production of Ang II could contribute to tubulointerstitial injury in this model.

Author List

Zimpelmann J, Kumar D, Levine DZ, Wehbi G, Imig JD, Navar LG, Burns KD

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Angiotensin Receptor Antagonists
Angiotensinogen
Animals
Antihypertensive Agents
Diabetes Mellitus, Experimental
Diabetic Nephropathies
Gene Expression
Hypertrophy
Hypoglycemic Agents
Insulin
Kidney Tubules, Proximal
Losartan
Male
Nephritis, Interstitial
RNA, Messenger
Rats
Rats, Sprague-Dawley
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin
Renin
Renin-Angiotensin System