Potassium control of extrarenal renin secretion  in transgenic (mRen-2)27 and normal rats

Rong, Pei; Wilkinson-Berka, Jennifer L; Skinner, Sandford L.

doi:10.1152/ajpendo.1999.277.4.e631

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…Ang I generated was estimated by radioimmunoassay with an in-house antibody and a 125 I-Ang I tracer. 24,25 In this assay, 1 GU of standard hog renin generated 87 g Ang I/h, a value similar to that found by Devaux et al 26 (68 g Ang I/h), although incubated at pH 6.5. For kinetic studies, renin and aogen were serially diluted with PBS with bovine serum albumin (see Results) and keeping incubate volume and protein concentration constant.…”

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confidence: 87%

“…Residual renin in plasma was removed by antibody affinity chromatography. 24 Rat aogen content was 7.8 mol/L and mouse content was 0.2 mol/L, estimated as the maximum Ang I generated during incubation with excess SMG renin in the presence of angiotensinase inhibitors (see following sections). The aogen was dialyzed against a phosphate (0.1 mol/L)/saline (0.05 mol/L) buffer (PBS), pH 7.4 at 4°C, and stored frozen at Ϫ20°C.…”

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Hypertension in the (mRen-2)27 Rat Is Not Explained by Enhanced Kinetics of Transgenic Ren-2 Renin

2003

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Abstract-Enhanced efficiency of the reaction between transgenic Ren-2 mouse renin and endogenous rat angiotensinogen has been suggested as 1 mechanism that contributes to the accelerated hypertension and increased tissue angiotensin of the (mRen-2)27 transgenic rat. This was tested in a study conducted at pH 7.4 in vitro that compared the kinetic constants of purified mouse Ren-2 and rat renin (each at 100, 75, 50, and 25 pmol/L) reacting with physiologic concentrations of rat angiotensinogen (0 to 4 mol/L). Under these conditions, the kinetic constants for Ren-2 (K m , 1.8 mol/L; K cat , 0.07/s; and K cat /K m , 0.04 L · mol Ϫ1 · s Ϫ1 ) were not different from rat renin. However, Ren-2 renin acting on its homologous mouse angiotensinogen was confirmed as being much slower. We conclude that hypertension in the Ren-2 rat is not related to renin kinetics. Other mechanisms are considered, with reference to human essential hypertension. Key Words: renin-angiotensin system Ⅲ angiotensinogen Ⅲ blood pressure Ⅲ hypertension, essential T he hypertensive (mRen-2)27 transgenic rat (Ren-2 rat) developed by Mullins et al 1 displays strong expression of the mouse Ren-2 transgene in several extrarenal tissues, 2 suppressed endogenous renal renin, and predominantly mouse inactive prorenin in the circulation secreted from extrarenal sources. [3][4][5] Most evidence indicates that it is the active component of mouse Ren-2 renin in tissues and plasma, reacting with the endogenous rat angiotensinogen (aogen), that induces and sustains the hypertension through conventional angiotensin II (Ang II)-dependent mechanisms, in particular because the hypertension is readily controlled by inhibition of the renin-angiotensin system (RAS). 6 However, this concept is at odds with the initial published evidence of suppressed or normal active plasma renin and angiotensin peptides in the adult Ren-2 rat, 1,7,8 reports that encouraged a search for additional hypertensive mechanisms. This transgenic rat strain has now been used widely to study various conditions relating to activation of the tissue RAS, including angiogenesis, cytokine activation, and profibrotic and inflammatory pathologic states, making it important to understand fully the fundamental processes inducing the severe hypertension.That plasma Ang II is not suppressed is now apparent, with resting levels increased up to 4-fold in both young 9 and adult 10 Ren-2 rats. One would expect a similar elevation of plasma active renin, but this depends on the pH at which the activity is estimated, 11,12 because mouse and rat renins have different pH optima when acting on rat aogen (pH 8.5 and 6.5, respectively). 5,11,12 Measured at pH 7.4 the Ren-2 rat plasma renin reaction is a mixed activity, mainly owing to the mouse transgenic renin, 11 and increases in renin activity have been found under these physiologic conditions. The lower level of rat renin in plasma is consistent with its low but not absent level in the kidneys. 11,12 By comparison with other high-renin models that cause malignant...

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Hypertension in the (mRen-2)27 Rat Is Not Explained by Enhanced Kinetics of Transgenic Ren-2 Renin

2003

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“…In turn, the terminal two amino acids of angiotensin I are cleaved by angiotensin-converting enzyme (ACE) to yield Ang II, the effector molecule of the renin-angiotensin system (RAS). The presence of a local, as distinct from a systemic RAS, has been established in several organs including the heart, adrenal gland, thymus and ovary [7, 8, 9, 10, 11, 12]. This is also true for the eye, following the identification of RAS components including angiotensinogen, renin and ACE within the eyes of humans, rats and other mammals [13, 14, 15, 16].…”

Section: The Ocular Renin-angiotensin System: Characterization and Nomentioning

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The Interaction between the Renin-Angiotensin System and Vascular Endothelial Growth Factor in the Pathogenesis of Retinal Neovascularization in Diabetes

Wilkinson-Berka

Kelly²,

Gilbert³

2001

J Vasc Res

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Despite the use of laser photocoagulation and knowledge of the beneficial effects of good glycaemic control, visual loss due to diabetic retinopathy remains the commonest cause of blindness in the working population. This visual loss is principally the result of proliferative diabetic retinopathy and macular oedema. The processes by which diabetes mellitus results in retinopathy are incompletely understood, but recent evidence has suggested a pathogenetic role for the renin-angiotensin system (RAS) and vascular endothelial growth factor (VEGF) in the eye in response to chronic hyperglycaemia. This review will explore evidence of a local RAS in the eye, the involvement of VEGF in diabetic retinopathy and the interaction between the RAS and VEGF in the pathogenesis of retinal neovascularization.

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Control of renin secretion from adrenal gland in transgenic Ren-2 and normal rats

Rong

Wilkinson-Berka

Skinner

2001

Molecular and Cellular Endocrinology

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Potassium control of extrarenal renin secretion in transgenic (mRen-2)27 and normal rats

Cited by 3 publications

References 28 publications

Hypertension in the (mRen-2)27 Rat Is Not Explained by Enhanced Kinetics of Transgenic Ren-2 Renin

Hypertension in the (mRen-2)27 Rat Is Not Explained by Enhanced Kinetics of Transgenic Ren-2 Renin

The Interaction between the Renin-Angiotensin System and Vascular Endothelial Growth Factor in the Pathogenesis of Retinal Neovascularization in Diabetes

Control of renin secretion from adrenal gland in transgenic Ren-2 and normal rats

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