Contribution of Renal Angiotensin Converting Enzyme(ACE) to Blood Pressure Regulation: Possible Role of Brush Border Ace

Ikemoto, Fumihiko; Itoh, Satoko; Song, Gyeong-Bu; Tanaka, Motoharu; Takada, Toyokazu; Tominaga, Munechika; Hiruma, Masahito; Nakamura, Norifumi; Yamamoto, Kenjiro

doi:10.3109/10641968709164211

Cited by 11 publications

(13 citation statements)

References 8 publications

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“…Furthermore, when we measured the expression of ACE mRNA in these organs, although no significant intra-group differences were evident for heart, lung and kidney, the aorta in the ALA group showed significantly lower expression than aorta from the control group ( ), thus reflecting the results for ACE activity. In accord with our results, Ikemoto et al have indicated that inhibition of ACE in the aorta coincides to a greater extent with the hypotensive effects of drugs 30) . Murakami et al also have demonstrated that treatment with an ACE inhibitor lowered both blood pressure and aortic ACE activity in stroke-prone SHR 31) .…”

Section: Discussionsupporting

confidence: 82%

Dietary Alpha-Linolenic Acid Inhibits Angiotensin-Converting Enzyme Activity and mRNA Expression Levels in the Aorta of Spontaneously Hypertensive Rats

et al. 2009

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Several studies have shown that dietary alpha-linolenic acid (ALA) is associated with a reduced risk of cardiovascular disease and has an antihypertensive effect. Blood pressure is regulated mainly by angiotensin-converting enzyme (ACE). In the present study, we investigated the effect of dietary ALA on ACE to clarify the mechanism of the antihypertensive effect in spontaneously hypertensive rats (SHR). Sixweek-old SHR were fed a diet containing either 10% ALA-rich flaxseed oil or high oleic safflower oil as a control for four weeks. Systolic blood pressure (SBP) was measured by the tail cuff method once weekly. At the end of the feeding period, ACE activity was determined in the heart, aorta, lung and kidney. ACE mRNA in these organs was also measured by real-time PCR analysis. SBP in the ALA group was significantly lower than in the control group at 2, 3, and 4 weeks. The ACE activity and mRNA expression levels in the ALA group were significantly lower than in the control only in the aorta. In conclusion, the present findings suggest that the blood pressure-lowering mechanism of dietary ALA may be involved in the reduction of ACE activity and mRNA expression levels in the aorta of SHR.

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Section: Discussionsupporting

confidence: 82%

Dietary Alpha-Linolenic Acid Inhibits Angiotensin-Converting Enzyme Activity and mRNA Expression Levels in the Aorta of Spontaneously Hypertensive Rats

et al. 2009

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“…In contrast, ACE expression was enhanced in renal tissues from diabetic hamsters, but was localized in the brush border of the proximal tubules (Fig. 1A), as shown in a previous study (20).…”

Section: Resultsmentioning

confidence: 56%

“…*P Ͻ 0.05, **P Ͻ 0.01 (ANOVA). chymases and tissue RAS (8,18,20). Here, we showed that chymase-specific inhibitor TEI-E00548 partially, and TEI-F00806 completely, prevented proteinuria and renal mesangial expansion in diabetic hamsters.…”

Section: Discussionmentioning

confidence: 76%

Inhibition of chymase protects against diabetes-induced oxidative stress and renal dysfunction in hamsters

Maeda

Inoguchi

Takei³

et al. 2010

American Journal of Physiology-Renal Physiology

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Inhibition of chymase protects against diabetes-induced oxidative stress and renal dysfunction in hamsters. Am J Physiol Renal Physiol 299: F1328 -F1338, 2010. First published September 29, 2010 doi:10.1152/ajprenal.00337.2010.-Accumulating evidence suggests that the intrarenal renin-angiotensin system may be involved in the progression of diabetic nephropathy. Chymase is a potent local angiotensin II-forming enzyme in several species, including humans and hamsters. However, the pathophysiological role of chymase is not fully understood. Here, we report a causal role of chymase in diabetic nephropathy and the therapeutic effectiveness of chymase inhibition. In the present study, renal chymase expression was markedly upregulated in streptozotocin-induced diabetic hamsters. Oral administration of a specific chymase inhibitor, TEI-F00806, completely ameliorated proteinuria, the overexpression of transforming growth factor-␤ and fibronectin in glomeruli, and renal mesangial expansion, by normalizing the increase in intrarenal angiotensin II levels in diabetic hamsters independently of blood pressure levels. In contrast, ramipril did not show such sufficient effects. These effects occurred in parallel with improvements in superoxide production and expression of NAD(P)H oxidase components [NAD(P)H oxidase 4 and p22 phox ] in glomeruli. This study showed for the first time that chymase inhibition may protect against elevated intrarenal angiotensin II levels, oxidative stress, and renal dysfunction in diabetes. These findings suggest that chymase offers a new therapeutic target for diabetic nephropathy.angiotensin II; NAD(P)H oxidase DIABETIC NEPHROPATHY IS A leading cause of renal failure worldwide and is associated with an increased risk of cardiovascular events. Experimental and clinical trials have indicated that blockade of the renin-angiotensin system (RAS) with angiotensin I-converting enzyme (ACE) inhibitors or angiotensin II (ANG II) antagonists has some protective effects on diabetic nephropathy and on cardiovascular events (3, 4, 32), which appear to be independent of its antihypertensive effect. These findings suggest that the intrarenal RAS may be involved in the progression of diabetic nephropathy. It is well recognized that the ACE-dependent ANG II-generating system is a source of intrarenal ANG II production. However, the use of ACE inhibitors was reported to only partly reduce the intrarenal ANG II production (10), suggesting the existence of alternative pathways. Indeed, human chymase specifically hydrolyzes the Phe 8 -His 9 bond in ANG I and forms ANG II (26). Tissue chymase of other several species including the hamster also have more efficient ANG II-forming activities than ACE, while rat chymase degrades ANG II inversely (1, 26). Of note, several reports have shown that chymase expression may be upregulated in diabetic renal tissues (14,19,29). However, it is still unclear whether chymase substantially contributes to the activation of intrarenal RAS in diabetic renal tissues. More importantly, th...

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“…As described before, ACE is abundantly expressed in the kidney, including the vascular endothelium as well as both the luminal and basolateral membranes of both proximal and distal tubules, but its activity is more abundant in the proximal tubule brush border and fluid (Erdös, 1990;Sibony et al, 1993;Casarini et al, 1997;Harrison-Bernard et al, 2002;Mezzano et al, 2003ab). Intrarenal ACE is involved in generating Ang II not only from systemically delivered Ang I but also from intrarenally generated Ang I in view of abundant ACE and angiotensinases found in brush border (Ward et al, 1976;Ikemoto et al, 1987;Erdös, 1990;Sibony et al, 1993;Casarini et al, 1997). Furthermore, Ang I directly added by perfusion into the peritubular capillaries is converted to Ang II and exerts afferent arteriolar vasoconstriction, decreases in single nephron glomerular filtration rate, and increases in proximal fractional reabsorption rate Navar, 1987, 1988).…”

Section: A Angiotensin-converting Enzyme Inhibitorsmentioning

confidence: 99%

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

et al. 2007

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Contribution of Renal Angiotensin Converting Enzyme(ACE) to Blood Pressure Regulation: Possible Role of Brush Border Ace

Cited by 11 publications

References 8 publications

Dietary Alpha-Linolenic Acid Inhibits Angiotensin-Converting Enzyme Activity and mRNA Expression Levels in the Aorta of Spontaneously Hypertensive Rats

Dietary Alpha-Linolenic Acid Inhibits Angiotensin-Converting Enzyme Activity and mRNA Expression Levels in the Aorta of Spontaneously Hypertensive Rats

Inhibition of chymase protects against diabetes-induced oxidative stress and renal dysfunction in hamsters

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

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