The Effect of Angiotensin II Receptor Blockade on an End-Stage Renal Failure Model of Type 2 Diabetes

Mizuno, Makoto; Sada, Toshio; Kato, Mikio; Fukushima, Yasuo; Terashima, Hiroyuki; Koike, Hiroyuki

doi:10.1097/01.fjc.0000245241.79959.d6

Cited by 35 publications

(36 citation statements)

References 19 publications

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“…MCP-1 is a macrophage chemokine that has been shown to have a key role in macrophage recruitment in several models of renal injury. [21][22][23] In addition to MCP-1, the induction of osteopontin expression in tubular cells in response to hypokalemia could play a role in macrophage recruitment. 24 -26 The second and more important discovery was the observation that there was progressive capillary loss in hypokalemic nephropathy.…”

Section: Discussionmentioning

confidence: 99%

Hypokalemic Nephropathy is Associated with Impaired Angiogenesis

Reungjui

Roncal

Sato

et al. 2008

Journal of the American Society of Nephrology

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Hypokalemic nephropathy is associated with alterations in intrarenal vasoactive substances, leading to vasoconstriction, salt-sensitivity, and progression of interstitial fibrosis. In this study, we investigated whether hypokalemic nephropathy might also involve impaired renal angiogenesis. Sprague-Dawley rats that were fed low-potassium diets developed peritubular capillary loss that began in the inner stripe of the outer medulla (week 2) and progressed to the outer stripe of the outer medulla (week 4) and cortex (week 12). These changes were associated with increased macrophage infiltration, increased expression of both monocyte chemoattractant protein-1 and TNF-␣, and a loss of vascular endothelial growth factor and endothelial nitric oxide synthase. Renal thiobarbituric acid-reactive substances, markers of oxidative stress, were increased late in disease. In conclusion, hypokalemic nephropathy is associated with impaired renal angiogenesis, evidenced by progressive capillary loss, reduced endothelial cell proliferation, and loss of VEGF expression.

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Section: Discussionmentioning

confidence: 99%

Hypokalemic Nephropathy is Associated with Impaired Angiogenesis

Reungjui

Roncal

Sato

et al. 2008

Journal of the American Society of Nephrology

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“…Progressive renal injury starts at 18 -20 wk of age and significant kidney damage is observed at 30 -35 wk of age, the average age of the ZDF rats in the present study. The majority of studies examining the effects of long-term treatment with inhibitors of the renin angiotensin system show that the diabetic-induced nephropathy is significantly reduced by inhibition of the renin angiotensin system in animals and patients with type 2 diabetes (4,5,28,33,35). In a limited study of four obese ZDF rats, we examined the effects of 12 wk of treatment with the converting enzyme inhibitor enalapril (400 mg⅐kg Ϫ1 ⅐diet Ϫ1 ), on the PGE 2 -mediated increase in substance P release.…”

Section: Discussionmentioning

confidence: 99%

“…There is the considerable evidence for increased angiotensin II activity in type 1 and type 2 diabetes and inhibitors of the renin angiotensin system are commonly used in diabetic patients to treat hypertension and other cardiovascular diseases, including diabetic nephropathy. (1,2,4,11,28,32,33).…”

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confidence: 99%

Impaired responsiveness of renal sensory nerves in streptozotocin-treated rats and obese Zucker diabetic fatty rats: role of angiotensin

Kopp¹,

Cicha²,

Yorek³

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Increasing afferent renal nerve activity decreases efferent renal nerve activity and increases urinary sodium excretion. Activation of renal pelvic mechanosensory nerves is impaired in streptozotocin (STZ)-treated rats (model of type 1 diabetes). Decreased activation of renal sensory nerves would lead to increased efferent renal nerve activity, sodium retention, and hypertension. We examined whether the reduced activation of renal sensory nerves in STZ rats was due to increased renal angiotensin activity and whether activation of the renal sensory nerves was impaired in obese Zucker diabetic fatty (ZDF) rats (model of type 2 diabetes). In an isolated renal pelvic wall preparation from rats treated with STZ for 2 wk, PGE2 failed to increase the release of substance P, from 5 ± 1 to 6 ± 1 pg/min. In pelvises from sham STZ rats, PGE2 increased substance P release from 6 ± 1 to 13 ± 2 pg/min. Adding losartan to the incubation bath increased PGE2-mediated release of substance P in STZ rats, from 5 ± 1 to 10 ± 2 pg/min, but had no effect in sham STZ rats. In pelvises from obese ZDF rats (22–46 wk old), PGE2 increased substance P release from 12.0 ± 1.2 to 18.3 ± 1.2 pg/min, which was less than that from lean ZDF rats (10.3 ± 1.6 to 22.5 ± 2.4 pg/min). Losartan had no effect on the PGE2-mediated substance P release in obese or lean ZDF rats. We conclude that the mechanisms involved in the decreased responsiveness of the renal sensory nerves in STZ rats involve activation of the renin angiotensin system in STZ but not in obese ZDF rats.

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“…Several large clinical studies and experimental studies matched with the natural clinical stage of diabetic nephropathy have been carried out for a decade. [2][3][4][5][6][7][8][9][10][11][12][13] Broken lines indicate the supposed course after starting interventional treatments of ARBs. An experimental model of metabolic syndrome is similar but not identical to diabetic nephropathy.…”

mentioning

confidence: 99%

“…Therefore, ARB for diabetic nephropathy has established an indispensable therapy in large-scale clinical studies [2][3][4][5][6][7][8] and stage-matched experimental studies. [9][10][11][12] Moreover, the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study is ongoing, and its purpose is to determine whether ARB would be able to prevent the occurrence of microalbuminuria in type II diabetic patients with normoalbuminuria. 13 The renin-angiotensin-aldosterone system (RAAS) in the kidney is believed to be involved in a crucial network that has influence in the development of renal injury.…”

mentioning

confidence: 99%