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Title: Renal expression of angiotensin receptors in long-term diabetes and the effects of angiotensin type 1 receptor blockade.
Austin Authors: Bonnet, Fabrice;Candido, Riccardo;Carey, Robert M;Casley, David J;Russo, Leileata M;Osicka, Tanya M;Cooper, Mark E;Cao, Zemin
Affiliation: Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg West, Victoria 3081, Australia
Issue Date: 1-Aug-2002
Publication information: Journal of Hypertension; 20(8): 1615-24
Abstract: The aims of this study were to assess the renal expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in diabetic spontaneously hypertensive rats (SHR) and the effect of AT1 receptor blockade on the expression of these receptors.Diabetes was induced by injection of streptozotocin in SHRs. Irbesartan, an AT1 receptor antagonist, was given to diabetic SHRs for 32 weeks (15 mg/kg per day, n = 10). Diabetic (n = 10) and non-diabetic SHRs (n = 10) were studied concurrently. A separate group of control and diabetic Wistar-Kyoto (WKY) rats were also evaluated.Gene and protein expressions of the AT1 and AT2 receptor were assessed by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry with specific antibodies andin vitro autoradiography with [125I]Sar(1), Ile(8) angiotensin II or [125I]CGP42112B.Both AT1 and AT2 receptor mRNA levels in the kidney were reduced in diabetic SHRs compared to non-diabetic SHRs. Immunohistochemistry staining with specific antibodies showed a similar reduction in glomerular and tubulo-interstitial staining for both AT1 and AT2 receptors. Reduced binding for the AT1 and AT2 receptor was found in the kidney of diabetic SHRs. Diabetic SHRs developed albuminuria and had glomerular and tubulo-interstitial injury, which were prevented by treatment with irbesartan. Reduced expression of the AT1 receptor, but not the AT2 receptor, in diabetic SHRs was prevented by treatment with irbesartan. In diabetic WKY rats no such reduction in AT1 expression was observed, although there was a trend for reduced AT2 receptor expression.These findings demonstrated that renal expression of both AT1 and AT2 receptor was reduced in long-term diabetic SHRs and that blockade of the AT1 receptor had disparate effects on expression of angiotensin II receptor subtypes.
Gov't Doc #: 12172324
Journal: Journal of Hypertension
Type: Journal Article
Subjects: Angiotensin Receptor Antagonists
Biphenyl Compounds.therapeutic use
Diabetes Mellitus, Experimental.drug therapy.genetics.metabolism.pathology
Diabetic Nephropathies.genetics.metabolism.pathology.prevention & control
Gene Expression.drug effects
Kidney.drug effects.metabolism.pathology
RNA, Messenger.genetics.metabolism
Rats, Inbred SHR
Rats, Inbred WKY
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin.genetics.metabolism
Tetrazoles.therapeutic use
Appears in Collections:Journal articles

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