Developmental Activity of the Renin-Angiotensin System during the "Critical Period" Modulates Later L-NAME-Induced Hypertension and Renal Injury

Introduction: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. Materials and methods: We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/–), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin–angiotensin system components in the laminal terminalis and peripheral organs. Results: Nestin-BDNF (+/–) mice had lower renin–angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin–angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension. Conclusion: Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin–angiotensin system molecules.

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The Intratubular and Intracrine Renin-Angiotensin System in the Proximal Tubules of the Kidney and Its Roles in Angiotensin II-Induced Hypertension

Selected Chapters from the Renin-Angiotensin System ◽

10.5772/intechopen.88054 ◽

2020 ◽

Author(s):

Xiao C. Li ◽

Ana Paula de Oliveira Leite ◽

Xu Chen ◽

Chunling Zhao ◽

Xiaowen Zheng ◽

...

Keyword(s):

Angiotensin Ii ◽

Renin Angiotensin System ◽

Proximal Tubules ◽

Angiotensin System ◽

Renin Angiotensin ◽

Induced Hypertension

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AT1 antagonism and renin inhibition in mice: pivotal role of targeting angiotensin II in chronic kidney disease

AJP Renal Physiology ◽

10.1152/ajprenal.00672.2011 ◽

2012 ◽

Vol 303 (7) ◽

pp. F1037-F1048 ◽

Cited By ~ 20

Author(s):

Christoph Fraune ◽

Sascha Lange ◽

Christian Krebs ◽

Alexandra Hölzel ◽

Jana Baucke ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Injury ◽

Plasma Concentrations ◽

Renin Angiotensin System ◽

Pivotal Role ◽

Angiotensin System ◽

Renin Angiotensin ◽

Renin Inhibition

The role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT1 antagonism ameliorate renal damage. However, it is unclear which mechanism exerts better nephroprotection. We compared the renin inhibitor aliskiren with the AT1 antagonist losartan in mice with chronic kidney disease due to renal ablation. Doses were adjusted to equipotent inhibition of the renin-angiotensin system, determined via a dose-response quantifying plasma and renal renin expression. Six-week treatment with either 500 mg/l drinking water losartan or 50 mg·kg−1·day−1 aliskiren significantly decreased albuminuria, glomerular damage, and transcription rates of renal injury markers to a similar extent. An array analysis comparing renal gene expression of losartan- and aliskiren-treated mice evaluating >34,000 transcripts demonstrated regulation for 14 genes only, with small differences. No superior nephroprotection was found by combining losartan and aliskiren. Compared with plasma concentrations, aliskiren accumulated ∼7- to 29-fold in the heart, liver, lung, and spleen and ∼156-fold in the kidney. After withdrawal, plasma concentrations dropped to zero within 24 h, whereas renal tissue concentrations declined slowly over days. Withdrawal of aliskiren in mice with chronic kidney disease revealed a significantly delayed re-increase in albuminuria compared with withdrawal of losartan. This study demonstrates equieffective nephroprotection of renin inhibition and AT1 antagonism in mice with chronic kidney disease without additional benefit of combination therapy. These observations underscore the pivotal role of targeting ANG II to reduce renal injury.

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Letter to the Editor: “Insulin Resistance, the Renin-Angiotensin System, and Associated Renal Injury: Is Insulin Resistance the Culprit?”

Renal Failure ◽

10.1080/08860220601039536 ◽

2007 ◽

Vol 29 (1) ◽

pp. 113-114

Author(s):

Mohamed H. Ahmed

Keyword(s):

Insulin Resistance ◽

Renal Injury ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

Letter To The Editor

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Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

AJP Renal Physiology ◽

10.1152/ajprenal.00477.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. F150-F157 ◽

Cited By ~ 48

Author(s):

Romer A. Gonzalez-Villalobos ◽

Ryousuke Satou ◽

Naro Ohashi ◽

Laura C. Semprun-Prieto ◽

Akemi Katsurada ◽

...

Keyword(s):

Renin Angiotensin System ◽

Ace Inhibition ◽

Ang Ii ◽

Male Mice ◽

Rt Pcr ◽

Angiotensin System ◽

Renin Angiotensin ◽

Induced Hypertension ◽

Angiotensin Type

Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls ( n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension.

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