Valsartan but not Atenolol Improves Vascular Pathology in Diabetic Ren-2 Rat Retina

Wilkinson-Berka, Jennifer L.; Tan, Genevieve; Jaworski, Kassie Ann; Ninkovic, Slavisa

doi:10.1016/j.amjhyper.2006.09.018

Cited by 51 publications

(47 citation statements)

References 34 publications

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“…In diabetic retinopathy, neoangiogenesis may be preceded by the presence of acellular capillaries, in which pericytes and endothelial cells are absent. Our finding that acellular capillaries develop in the mid and peripheral retina of diabetic Ren-2 rats is consistent with our previous studies [24], and with observations in diabetic patients [33]. As rodents do not develop retinal neoangiogenesis, even after years of diabetes [34], we also studied OIR [22].…”

Section: Discussionsupporting

confidence: 78%

“…These findings are consistent with our previous studies in diabetic Ren-2 rats where we compared ARB with the β-blocker, atenolol. Both treatments normalised BP in diabetic Ren-2 rats; however, only ARB reduced retinal vasculopathy and improved the electroretinogram [24,38]. Similar comparisons in OIR may not necessarily be informative given that β-blockers have anti-proliferative effects in OIR [39], and whether this occurs by a BPdependent mechanism is uncertain as BP cannot be measured in P18 rodents.…”

Section: Discussionmentioning

confidence: 99%

“…Acellular capillaries in diabetic Ren-2 rats Acellular capillaries were counted in trypsin digests of retina as previously described [24]. Separate quantification was performed for central retina (0 to 1,666±166 μm from the optic disc), mid retina (1,667 to 3,050±154 μm) and peripheral retina (3, Neoangiogenesis in OIR Eyes were processed into paraffin, serially sectioned at 3 μm, and blood vessel profiles (BVPs) quantified in four non-overlapping fields of retina/section, with six sections/retina at least 60 μm apart evaluated per rat [9].…”

Section: Animals Procedures Complied With the Alfred Medicalmentioning

confidence: 99%

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Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

et al. 2011

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Aim/hypothesis We examined whether the renin inhibitor, aliskiren, provides similar or greater protection than ACE inhibition from non-proliferative diabetic retinopathy and from the proliferative neoangiogenesis of oxygen-induced retinopathy. Methods Transgenic (mRen-2)27 rats, which overexpress mouse renin and angiotensin in extra-renal tissues, were studied. For diabetic studies, non-diabetic, diabetic (streptozotocin, 55 mg/kg), diabetic + aliskiren (10 mg kg −1 day −1 , pump), or diabetic + lisinopril (10 mg kg −1 day −1 , drinking water) rats were evaluated over 16 weeks. For oxygeninduced retinopathy studies, rats were exposed to 80% oxygen (22 h/day) from postnatal days 0 to 11, and then room air from postnatal days 12 to 18. Aliskiren (10 or 30 mg kg −1 day −1 , pump) or lisinopril (10 mg kg −1 day −1 , drinking water) was administered during retinopathy development between postnatal days 12 and 18. Results Systolic BP in diabetic (mRen-2)27 rats was reduced with 10 mg kg −1 day −1 aliskiren, but only lisinopril normalised systolic blood pressure. In diabetic (mRen-2)27 rats, 10 mg kg −1 day −1 aliskiren and lisinopril reduced retinal acellular capillaries and leucostasis to non-diabetic levels. In oxygen-induced retinopathy, neoangiogenesis and retinal inflammation (leucostasis, ED-1 immunolabelling) were partially reduced by 10 mg kg −1 day −1 aliskiren and normalised by 30 mg kg −1 day −1 aliskiren, whereas lisinopril normalised neoangiogenesis and reduced leucostasis and ED-1 immunolabelling. Aliskiren and lisinopril normalised retinal vascular endothelial growth factor expression; however, only aliskiren reduced intercellular adhesion molecule-1 to control levels. Conclusions/interpretation Aliskiren provided similar or greater retinal protection than ACE inhibition and may be a potential treatment for diabetic retinopathy.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Animals Procedures Complied With the Alfred Medicalmentioning

confidence: 99%

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Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

et al. 2011

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“…Rats were killed at P18 with sodium pentobarbitone (170 mg/mL, Virbac, Peakhurst, New South Wales, Australia). Doses of FAD286 and valsartan were based on previous studies indicating amelioration of organ pathology 12,24 with a concomitant reduction in circulating aldosterone (FAD286) 24 and increase in circulating renin (valsartan), 12 without any detrimental effects on animal health and survival. In the present study, body weight was not influenced by FAD286 and slightly increased by valsartan (in the online-only Data Supplement and Table S1).…”

Section: Animalsmentioning

confidence: 99%

Neovascularization Is Attenuated With Aldosterone Synthase Inhibition in Rats With Retinopathy

et al. 2012

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Abstract-Neovascularization is a hallmark feature of retinopathy of prematurity and diabetic retinopathy. Type 1 angiotensin receptor blockade reduces neovascularization in experimental retinopathy of prematurity, known as oxygen-induced retinopathy (OIR). We investigated in OIR whether inhibiting aldosterone with the aldosterone synthase inhibitor FAD286 reduced neovascularization as effectively as angiotensin receptor blockade (valsartan). OIR was induced in neonatal Sprague-Dawley rats, and they were treated with FAD286 (30 mg/kg per day), valsartan (10 mg/kg per day), or FAD286ϩvalsartan. The cellular sources of aldosterone synthase, the mineralocorticoid receptor, and 11␤-hydroxysteroid dehydrogenase 2 were evaluated in retinal cells involved in neovascularization (primary endothelial cells, pericytes, microglia, ganglion cells, and glia). In OIR, FAD286 reduced neovascularization and neovascular tufts by 89% and 67%, respectively, and normalized the increase in vascular endothelial growth factor mRNA (1.74-fold) and protein (4.74-fold) and was as effective as valsartan and FAD286ϩvalsartan. In retina, aldosterone synthase mRNA was reduced with FAD286 but not valsartan. Aldosterone synthase was detected in microglia, ganglion cells, and glia, whereas mineralocorticoid receptor and 11␤-hydroxysteroid dehydrogenase 2 were present in all of the cell types studied. Given the location of aldosterone synthase in microglia and their contribution to retinal inflammation and neovascularization in OIR, the effects of FAD286 on microglial density were studied. The increase in microglial density (ionized calcium binding adaptor protein 1 immunolabeling) in OIR was reduced with all of the treatments. In OIR, FAD286 reduced the increase in mRNA for tumor necrosis factor-␣, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and monocyte chemoattractant molecule 1. These findings indicate that aldosterone inhibition may be a potential treatment for retinal neovascularization.

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“…Acellular capillaries, defined as basement membrane tubes lacking cell nuclei and maintaining at least one fourth the normal capillary caliber over their lengths, were counted in a double-masked manner. (22) Quantitation was performed in 5 nonoverlapping microscopic fi elds chosen randomly from each eye. Results were expressed as acellular capillaries per field of retinal vascular network.…”

Section: Trypsin Digest Methods and Morphology Studiesmentioning

confidence: 99%

Jiangtang Xiaozhi Recipe (降糖消脂方) prevents diabetic retinopathy in streptozotocin-induced diabetic rats

Zhou

et al. 2016

Chin. J. Integr. Med.

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Valsartan but not Atenolol Improves Vascular Pathology in Diabetic Ren-2 Rat Retina

Abstract: Blockade of the renin-angiotensin system but not antihypertensive therapy with atenolol reduces vascular pathology in diabetic Ren-2 retina, suggesting that angiotensin II is a causative factor and therapeutic target in diabetic retinopathy.

Cited by 51 publications

References 34 publications

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

Neovascularization Is Attenuated With Aldosterone Synthase Inhibition in Rats With Retinopathy

Jiangtang Xiaozhi Recipe (降糖消脂方) prevents diabetic retinopathy in streptozotocin-induced diabetic rats

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