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Br J Pharmacol. 2008 May;154(1):136-43. doi: 10.1038/bjp.2008.48. Epub 2008 Mar 3.

Retinal plasma extravasation in streptozotocin-diabetic rats mediated by kinin B(1) and B(2) receptors.

Author information

1
Guy-Bernier Research Centre, Maisonneuve-Rosemont Hospital, Montréal, Canada.

Abstract

BACKGROUND AND PURPOSE:

We investigated whether or not kinin receptors play a role in diabetic blood-retinal barrier breakdown, which is a leading cause of vision loss.

EXPERIMENTAL APPROACH:

Blood-retinal barrier breakdown was quantified using Evans blue, and expression of kinin B(1) receptor mRNA was measured using quantitative reverse transcrition-PCR. Diabetic rats (streptozotocin (STZ), 65 mg kg(-1)) received a single intraocular injection of bradykinin (BK) or des-Arg(9)-BK, alone, or in combination with antagonists for B(1) (des-Arg(10)-Hoe140, R-715) and/or B(2) (Hoe140) receptors, given intraocularly or intravenously (i.v.).

KEY RESULTS:

In control rats, BK (0.1-10 nmol) dose-dependently increased plasma extravasation, which was inhibited by Hoe140 (0.2 nmol), whereas des-Arg(9)-BK (0.1 and 1 nmol) was without effect. B(1) receptor mRNA was markedly increased in retinas of diabetic rats, and this was prevented by N-acetyl-L-cysteine (1 g kg(-1) day(-1) for 7 days). Plasma extravasation in retinas of STZ-diabetic rats was higher than in controls and enhanced by des-Arg(9)-BK. Response to des-Arg(9)-BK was inhibited by intraocular or i.v. injection of B(1) receptor antagonists. Diabetes-induced plasma extravasation was inhibited only by a combination of des-Arg(10)-Hoe140 and Hoe 140 (100 nmol kg(-1), i.v. 15 min earlier) or by R-715 (1 micromol kg(-1), i.v.) injected daily for 7 days.

CONCLUSIONS AND IMPLICATIONS:

Kinin B(1) receptors are upregulated in retinas of STZ-diabetic rats through a mechanism involving oxidative stress. Both kinin B(1) and B(2) receptors contribute to increased plasma extravasation in diabetic retinopathy. Chronic inhibition of both kinin receptors, possibly with antioxidant adjuvants, may be a novel therapeutic strategy for diabetic retinopathy.

PMID:
18311190
PMCID:
PMC2438974
DOI:
10.1038/bjp.2008.48
[Indexed for MEDLINE]
Free PMC Article

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