Retinal angiotensin II and angiotensin-(1-7) response to hyperglycemia and an intervention with captopril

• Published in: Journal of the renin-angiotensin-aldosterone system 2018-07, Vol.19 (3), p.1470320318789323-1470320318789323
• Main Authors: Senanayake, Preenie deS, Bonilha, Vera L, W Peterson, John, Yamada, Yoshiro, Karnik, Sadashiva S, Daneshgari, Firouz, Brosnihan, K Bridget, Hollyfield, Joe G
• Format: Article
• Language: English
• Subjects: Angiotensin I - metabolism; Angiotensin II - metabolism; Animals; Blood Glucose - metabolism; Body Weight; Captopril - pharmacology; Captopril - therapeutic use; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - pathology; Diabetic retinopathy; Female; Hyperglycemia; Hyperglycemia - metabolism; Hyperglycemia - pathology; Original; Peptide Fragments - metabolism; Rats, Sprague-Dawley; Retina - drug effects; Retina - metabolism; Retina - pathology
• ISSN: 1470-3203; 1752-8976
• DOI: 10.1177/1470320318789323

Hypothesis: Hyperglycemia decreases angiotensin-(1-7), the endogenous counter-regulator of angiotensin II in the retina. Materials and methods: The distribution and levels of retinal angiotensin II (Ang II) and angiotensin-(1-7) (Ang-(1-7)) were evaluated by confocal imaging and quantitative immunohistochemistry during the development of streptozotocin-induced diabetes in rats. Results: In the nondiabetic eye, Ang II was localized to the endfeet of Müller cells, extending into the cellular processes of the inner plexiform layer and inner nuclear layer; Ang-(1-7) showed a wider distribution, extending from the foot plates of the Müller cells to the photoreceptor layer. Eyes from diabetic animals showed a higher intensity and extent of Ang II staining compared with nondiabetic eyes, but lower intensity with a reduced distribution of Ang-(1-7) immunoreactivity. Treatment of the diabetic animals with the angiotensin-converting enzyme inhibitor (ACEI) captopril showed a reduced intensity of Ang II staining, whereas increased intensity and distribution were evident with Ang-(1-7) staining. Conclusions: These studies reveal that pharmacological inhibition with ACEIs may provide a specific intervention for the management of the diabetes-induced decline in retinal function, reversing the profile of the endogenous angiotensin peptides closer to the normal condition.