Effects of Dietary Sodium and Genetic Background on Angiotensinogen and Renin in Mouse

Lantelme, Pierre; Rohrwasser, Andreas; Gociman, Barbu; Hillas, Elaine; Cheng, Tong; Petty, G.A.; Thomas, J. Hywel; Xiao, Sha; Ishigami, Tomoaki; Herrmann, Tracy; Terreros, Daniel; Ward, Kenneth; Lalouel, Jean-Marc

doi:10.1161/01.hyp.0000016177.20565.a0

Cited by 98 publications

(102 citation statements)

References 32 publications

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“…In two mouse strains, angiotensinogen protein has been detected in urine. Water deprivation induced significant activation of tubular expression of angiotensinogen [73]. These data support the hypothesis that the intratubular angiotensinogen functionally exists and is regulated by pathophysiological conditions.…”

Section: Angiotensinogensupporting

confidence: 82%

“…Renin expression in connecting tubules was increased by sodium restriction [72]. Water deprivation induced significant activation in the tubular expression of renin [73]. These data support the hypothesis that intratubular renin functionally exists and is also regulated by pathophysiological conditions.…”

Section: Reninsupporting

confidence: 76%

“…Lalouel and colleagues [72,73] have focused on intratubular RAS. Confluent monolayers of conditionally immortalized cells of murine proximal tubules were grown on semipermeable membranes separating apical and basolateral compartments.…”

Section: Angiotensinogenmentioning

confidence: 99%

“…In addition to renin formed by the JGA cells, renin is synthesized by principal cells of connecting tubules and cortical collecting ducts [72,73]. Renin expression in connecting tubules was increased by sodium restriction [72].…”

Section: Reninmentioning

confidence: 99%

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Renal Renin-Angiotensin System

Ichihara

Kobori

Nishiyama

et al. 2004

Contributions to Nephrology

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The cardinal role of the intrarenal renin-angiotensin system (RAS) in the control of sodium excretion and the pathophysiology of hypertension continues to receive increased attention. In addition to its very powerful vasoconstrictor action, angiotensin (Ang) II exerts important actions on tubular transport function and several recent studies have emphasized the potential importance of actions of angiotensin peptides on receptors localized to the luminal membranes of both proximal and distal nephron segments. Furthermore, a strong case is being developed supporting the importance of local mechanisms regulating the activity of the RAS. This is due to the fact that all components of the RAS are strongly expressed in the kidneys.

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Section: Angiotensinogensupporting

confidence: 82%

Section: Reninsupporting

confidence: 76%

Section: Angiotensinogenmentioning

confidence: 99%

Section: Reninmentioning

confidence: 99%

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Renal Renin-Angiotensin System

Ichihara

Kobori

Nishiyama

et al. 2004

Contributions to Nephrology

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“…Measurements of plasma AGT, PRA and aldosterone AGT was measured by radioimmunoassay (RIA) as the release of AI after complete digestion by highly purified renin (Lantelme et al 2002). PRA was measured by RIA as Fig.…”

Section: Animal Protocolsmentioning

confidence: 99%

Response to genetic manipulations of liver angiotensinogen in the physiological range

et al. 2008

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Genetic variation in the human angiotensinogen gene (AGT) influences plasma AGT concentration and susceptibility to essential hypertension by a mechanism that remains to be clarified. When one or two additional copies of the gene were inserted by gene titration (by homologous recombination with gap-repair at the AGT locus), both plasma AGT and arterial pressure were elevated in the physiological range in the mouse. The causal dependency between plasma AGT and blood pressure and the relative contribution of the various tissues that express AGT to these two phenotypic parameters remained to be determined. To address these issues, we generated a transgenic mouse with overexpression of the mouse AGT gene restricted to the liver. The transgene was examined in two contrasted genetic backgrounds, the sodium-sensitive C57BL/6J and the sodium-resistant A/J. Transgenic and control male animals underwent continuous cardiovascular monitoring by telemetry for 14 days while under a standard sodium diet (0.2%). Moderate but significant increases in plasma AGT (40%, p = 0.01) and systolic blood pressure (4-6 mmHg, p ranging from 0.01 to \0.001) were observed in the sodium-sensitive background, but not in the sodium-resistant animals. Statistical analysis of a large number of consecutive, repeated measurements of blood pressure afforded power to detect small effects in the physiological range by use of advanced mixed models of analysis of variances and covariances. Although plasma renin activity was increased in the sodium-sensitive background, it did not reach statistical significance. These observations underline a potential contribution of systemic AGT to the mechanism of AGT-mediated hypertension, but the significance of sodium sensitivity in the genetic background suggests participation of the kidney in expression of the elevated blood pressure phenotype, a matter that will warrant further studies. They also highlight the challenge of identifying the contribution of individual genes in complex inheritance, as their effects are modulated by other genetic and environmental determinants.

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