Acute renal vascular response to ACE inhibition in two rat strains with different susceptibility to the development of glomerulosclerosis

Westenend, Pj; Smits, J. F. M.; Struyker‐Boudier, H. A. J.; Weening, Jan J.

doi:10.1093/ndt/7.7.602

Cited by 3 publications

(1 citation statement)

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“…Part of the difference between the previous and current studies may be explained by the use of younger Wistar rats (6 wk of age) in their original report (21). Strain differences between Wistar and WKY rats in terms of tissue peptide concentrations, particularly related to the kidney, have been documented previously (30). The differences in tissue concentration within these strains imply differential regulation of locally generated biologically active peptides (15).…”

Section: Discussionmentioning

confidence: 72%

Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

Jessup¹,

Trask²,

Chappell³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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A low expression of angiotensinogen in the heart has been construed as indicating a circulating uptake mechanism to explain the local effects of angiotensin II on tissues. The recent identification of angiotensin-(1-12) in an array of rat organs suggests this propeptide may be an alternate substrate for local angiotensin production. To test this hypothesis, tissues from 11-wk-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (n ϭ 14) were stained with purified antibodies directed to the COOH terminus of angiotensin-(1-12). Robust angiotensin-(1-12) staining was predominantly found in ventricular myocytes with less staining found in the medial layer of intracoronary arteries and vascular endothelium. In addition, angiotensin-(1-12) immunoreactivity was present in the proximal, distal, and collecting renal tubules within the deep cortical and outer medullary zones in both strains. Preadsorption of the antibody with angiotensin-(1-12) abolished staining in both tissues. Corresponding tissue measurements by radioimmunoassay showed 47% higher levels of angiotensin-(1-12) in the heart of SHR compared with WKY rats (P Ͻ 0.05). In contrast, renal angiotensin-(1-12) levels were 16.5% lower in SHR compared with the WKY rats (P Ͻ 0.05). This study shows for first time the localization of angiotensin-(1-12) in both cardiac myocytes and renal tubular components of WKY and SHR. In addition, we show that increased cardiac angiotensin-(1-12) concentrations in SHR is associated with a small, but statistically significant, reduction in renal angiotensin-(1-12) levels.angiotensinogen; angiotensin I; angiotensin II; hypertension; renin ALTHOUGH NUMEROUS STUDIES have documented the presence of a local renin-angiotensin system (RAS

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Section: Discussionmentioning

confidence: 72%

Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

Jessup¹,

Trask²,

Chappell³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Effects of early and late antihypertensive treatment on extracellular matrix proteins and mononuclear cells in uninephrectomized SHR

Geiger

Fierlbeck

Mai

et al. 1997

Kidney International

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The efficacy of an early and late treatment with the angiotensin converting enzyme inhibitor lisinopril or the angiotensin II receptor blocker ICI D8731 was investigated in uninephrectomized spontaneously hypertensive rats (SHR). Rats that underwent uninephrectomy (UNX) at six weeks of age were randomly assigned to receive no treatment, lisinopril shortly after UNX, lisinopril starting 16 weeks after UNX, ICI D8731 shortly after UNX, and ICI D8731 starting 16 weeks after UNX. Blood pressure was normalized with both treatments. After six months inulin clearance was not significant different, while proteinuria and prevalence of interstitial fibrosis were significantly reduced in all treatment groups. Immunohistochemical studies revealed an interstitial, periglomerular and perivascular increase of extracellular matrix proteins in all rats, but a markedly reduced expression of collagen I, IV and fibronectin after early and late treatment compared to untreated controls. We found a significant reduction of infiltrating macrophages and T-lymphocytes in all treated animals compared to untreated controls after 2, 4 and 6 months. Especially early treatment was associated with lower numbers of infiltrating cells. Both treatments reduced proliferation of tubular and interstitial cells. There were no striking differences with regard to nephroprotection between the ACE inhibitor and angiotensin II receptor blocker. These findings show that both treatments have beneficial effects on kidney structure and function. They suggest that both ACE inhibition and angiotensin II blockade decrease renal cell proliferation and suppress the infiltration of mononuclear cells that may trigger expression of extracellular matrix proteins and progressive nephrosclerosis.

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Systemic Factors Are Involved in the Pathogenesis of Proteinuria-Induced Glomerulosclerosis in Adriamycin Nephrotic Rats

Boer¹,

Navis

Tiebosch

et al. 1999

Journal of the American Society of Nephrology

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Abstract. This study aims to dissociate the respective roles of systemic nephrosis and of the intrarenal effects of proteinuria in the pathogenesis of focal segmental glomerulosclerosis (FGS) in adriamycin nephrosis. To this purpose, this study examined proteinuria and FGS in bilateral (BAP) and unilateral proteinuria (UAP) in two different rat strains. UAP was obtained by protecting one kidney from exposure to adriamycin by temporary clipping of one renal artery during adriamycin injection. At sacrifice (week 12), FGS was present in BAP and in exposed kidneys in UAP, but not in unexposed kidneys. FGS correlated significantly with proteinuria per kidney in BAP and UAP. Remarkably, for a given proteinuria per kidney, the sclerosis score was higher in BAP than in UAP, reflected by a higher ratio of FGS score per mg proteinuria per kidney (Wistar: 0.09 ± 0.01 in BAP versus 0.05 ± 0.01%/mg protein per d in UAP, P < 0.05; Lewis: 0.12 ± 0.01 in BAP versus 0.07 ± 0.01%/mg protein per d in UAP, P < 0.05), indicating that the local damaging effects of proteinuria are modified by other factors. Cholesterol correlated with total proteinuria in BAP and UAP. FGS score was positively correlated with cholesterol. The latter correlation was similar in BAP and UAP, indicating that cholesterol was a more uniform predictor for FGS than proteinuria per kidney. This was independent of strain-specific factors. On multilinear regression analysis, cholesterol turned out to be the most consistent predictor of FGS in proteinuric kidneys, with a stronger predictive value than proteinuria per kidney. It is concluded that although systemic sequelae of nephrosis do not induce renal damage in nonproteinuric kidneys, they modify the severity of proteinuria-induced FGS in proteinuric kidneys.

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Acute renal vascular response to ACE inhibition in two rat strains with different susceptibility to the development of glomerulosclerosis

Cited by 3 publications

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Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

Localization of the novel angiotensin peptide, angiotensin-(1-12), in heart and kidney of hypertensive and normotensive rats

Effects of early and late antihypertensive treatment on extracellular matrix proteins and mononuclear cells in uninephrectomized SHR

Systemic Factors Are Involved in the Pathogenesis of Proteinuria-Induced Glomerulosclerosis in Adriamycin Nephrotic Rats

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