Is there a local renin–angiotensin system in the heart?

Danser, A.H. Jan; Saris, Jasper J.; Schuijt, Martin P; Kats, Jorge P. van

doi:10.1016/s0008-6363(99)00202-3

Cited by 77 publications

(55 citation statements)

References 102 publications

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“…Tissue content of ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Sections of the left ventricle of WKY and SHR were processed for ANG-(1-12) peptide content using the specific ANG-(1-12) antibody generated by Nagata et al (20).…”

Section: Resultsmentioning

confidence: 99%

“…Immunohistochemistry was performed using two separate polyclonal antibodies directed to the COOH-terminus of the rat ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) One provided by Dr. Kato (University of Miyazaki, Japan) was affinity purified and previously characterized as having no cross-reactivity with smaller angiotensin fragments (20). The second antibody, prepared for us by AnaSpec (San Jose, CA), was IgG purified using protein A.…”

Section: Animalsmentioning

confidence: 99%

“…This analysis showed that neither antibody cross-reacted with any of the cellular proteins ranging in size from 20 -120 kDa. Additionally, we evaluated the ability of ANG I, ANG II, or ANG-(1-7) to bind both ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) antibodies in competition studies using 125 I-ANG-(1-12) peptide. These binding assays showed no cross-reactivity with ANG I (0.032% cross-reactivity), ANG II (Ͻ0.001% cross-reactivity), or ANG-(1-7).…”

Section: Animalsmentioning

confidence: 99%

“…These data have been interpreted as suggesting that the endogenous production of tissue ANG II may result from Aogen uptake from the circulation (8). With the discovery of angiotensin- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) [ANG- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)], first identified by Nagata et al (20), we hypothesized that this novel propeptide, cleaved from the Aogen protein, may be an alternate precursor for the local production of angiotensins facilitating intra-or paracrine RAS functions (25). With this in mind, this study characterized for the first time the expression and localization of ANG-(1-12) within cardiac and renal tissue of both normotensive and hypertensive rats using the combined procedures of immunohistochemistry and tissue peptide measures by radioimmunoassay (RIA).…”

mentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…AngII is usually produced in the bloodstream by the action of renin on angiotensinogen to form AngI, which is further cleaved by ACE to form AngII. However, organ-specific production of AngII has also been recognized in various organs, such as kidney and heart (3,4), and such local production seems to be unrelated to the systemic release of AngII (4,5). There is evidence that local tissue contents and interstitial fluid concentrations of AngII in the kidney are far greater than can be explained solely on the basis of equilibration with circulating concentrations (6 -8).…”

mentioning

confidence: 99%

Urinary Angiotensinogen as a Marker of Intrarenal Angiotensin II Activity Associated with Deterioration of Renal Function in Patients with Chronic Kidney Disease

Yamamoto

Nakagawa

Suzuki

et al. 2007

Journal of the American Society of Nephrology

178

185

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In chronic kidney disease (CKD), enhanced intrarenal angiotensin II (AngII) is involved in deterioration of renal function, but it is difficult to measure it. For assessment of the potential of urinary angiotensinogen as a marker of intrarenal AngII activity, the correlation of plasma and urinary renin-angiotensin system components, including angiotensinogen, with deterioration of renal function was investigated in 80 patients who had CKD and were not treated with AngII blocking agents. Changes that were induced by 14 d of losartan treatment (25 mg/d) were also measured in 28 patients. Angiotensinogen was measured by RIA of AngI after incubation with renin. Urinary angiotensinogen levels were greater in patients with low estimated GFR and elevated urinary protein and type IV collagen and correlated with renal AngII and type I collagen immunostaining intensities. The risk for deterioration of renal function (i.e., estimated GFR decline of >2.5 ml/min per yr) during a mean follow-up period of 23 mo (maximum 43 mo) was associated with urinary angiotensinogen of >3.0 nmol AngI equivalent per 1 g of urinary creatinine (AngI Eq/g Cre) at enrollment (hazard ratio 3.52). The event-free survival for deterioration of renal function was better in patients with urinary angiotensinogen <3.0 nmol AngI Eq/g Cre than those >3.0 nmol AngI Eq/g Cre. Losartan reduced urinary and plasma angiotensinogen, urinary protein and type IV collagen, and systolic BP, despite concomitant increases in plasma renin and AngII. These data suggest that urinary angiotensinogen is a potentially suitable marker of intrarenal AngII activity associated with increased risk for deterioration of renal function in patients with CKD.

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