Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage

Pablo Nakagawa; Anand R Nair; Larry N Agbor; Javier Gomez; Jing Wu; Shao Yang Zhang; Ko-Ting Lu; Donald A Morgan; Kamal Rahmouni; Justin L Grobe; Curt D Sigmund

doi:10.1161/HYPERTENSIONAHA.120.14972

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Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage

Journal article

Open access

Peer reviewed

Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage

Pablo Nakagawa, Anand R Nair, Larry N Agbor, Javier Gomez, Jing Wu, Shao Yang Zhang, Ko-Ting Lu, Donald A Morgan, Kamal Rahmouni, Justin L Grobe, …

Hypertension (Dallas, Tex. 1979), Vol.76(2), pp.468-477

08/2020

DOI: 10.1161/HYPERTENSIONAHA.120.14972

PMCID: PMC7347438

PMID: 32507043

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Abstract

Several cardiac and renal diseases are attributed to a dysregulation of the renin-angiotensin system. Renin, the rate-limiting enzyme of the renin-angiotensin system, has 2 isoforms. The classical renin isoform (renin-a) encoding preprorenin is mainly confined to the juxtaglomerular cells and released into the circulation upon stimulation. Alternatively, renin-b is predicted to remain intracellular and is expressed in the brain, heart, and adrenal gland. In the brain, ablation of renin-b (Ren-b mice) results in increased brain renin-angiotensin system activity. However, the consequences of renin-b ablation in tissues outside the brain remain unknown. Therefore, we hypothesized that renin-b protects from hypertensive cardiac and renal end-organ damage in mice. Ren-b mice exhibited normal blood pressure at baseline. Thus, we induced hypertension by using a slow pressor dose of Ang II (angiotensin II). Ang II increased blood pressure in both wild type and Ren-b to the same degree. Although the blood pressure between Ren-b and wild-type mice was elevated equally, 4-week infusion of Ang II resulted in exacerbated cardiac remodeling in Ren-b mice compared with wild type. Ren-b mice also exhibited a modest increase in renal glomerular matrix deposition, elevated plasma aldosterone, and a modestly enhanced dipsogenic response to Ang II. Interestingly, ablation of renin-b strongly suppressed plasma renin, but renal cortical renin mRNA was preserved. Altogether, these data indicate that renin-b might play a protective role in the heart, and thus renin-b could be a potential target to treat hypertensive heart disease.

Renin - metabolism

Genetic Predisposition to Disease

Male

Renin-Angiotensin System - physiology

Renin - blood

Hypertension - metabolism

Mice, Knockout

Kidney - metabolism

Renin - genetics

Animals

Protein Isoforms - metabolism

Hypertension - chemically induced

Blood Pressure - physiology

Mice

Hypertension - genetics

Angiotensin II

Protein Isoforms - genetics

Details

Title: Subtitle: Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage
Creators: Pablo Nakagawa - From the Department of Physiology, Medical College of Wisconsin, Milwaukee (P.N., J.G., J.W., K.-T.L., J.L.G., C.D.S.)
Anand R Nair - Department of Neuroscience and Pharmacology, Roy J. and Lucille. Carver College of Medicine, University of Iowa (A.R.N., L.A., S.Y.Z., D.A.M., K.R.)
Larry N Agbor - Department of Neuroscience and Pharmacology, Roy J. and Lucille. Carver College of Medicine, University of Iowa (A.R.N., L.A., S.Y.Z., D.A.M., K.R.)
Javier Gomez - From the Department of Physiology, Medical College of Wisconsin, Milwaukee (P.N., J.G., J.W., K.-T.L., J.L.G., C.D.S.)
Jing Wu - From the Department of Physiology, Medical College of Wisconsin, Milwaukee (P.N., J.G., J.W., K.-T.L., J.L.G., C.D.S.)
Shao Yang Zhang - Department of Neuroscience and Pharmacology, Roy J. and Lucille. Carver College of Medicine, University of Iowa (A.R.N., L.A., S.Y.Z., D.A.M., K.R.)
Ko-Ting Lu - From the Department of Physiology, Medical College of Wisconsin, Milwaukee (P.N., J.G., J.W., K.-T.L., J.L.G., C.D.S.)
Donald A Morgan - Department of Neuroscience and Pharmacology, Roy J. and Lucille. Carver College of Medicine, University of Iowa (A.R.N., L.A., S.Y.Z., D.A.M., K.R.)
Kamal Rahmouni - Department of Neuroscience and Pharmacology, Roy J. and Lucille. Carver College of Medicine, University of Iowa (A.R.N., L.A., S.Y.Z., D.A.M., K.R.)
Justin L Grobe - From the Department of Physiology, Medical College of Wisconsin, Milwaukee (P.N., J.G., J.W., K.-T.L., J.L.G., C.D.S.)
Curt D Sigmund - From the Department of Physiology, Medical College of Wisconsin, Milwaukee (P.N., J.G., J.W., K.-T.L., J.L.G., C.D.S.)
Resource Type: Journal article
Publication Details: Hypertension (Dallas, Tex. 1979), Vol.76(2), pp.468-477
DOI: 10.1161/HYPERTENSIONAHA.120.14972
PMID: 32507043
PMCID: PMC7347438
NLM abbreviation: Hypertension
ISSN: 0194-911X
eISSN: 1524-4563
Publisher: United States
Grant note: T32 HL007121 / NHLBI NIH HHS R35 HL144807 / NHLBI NIH HHS K01 HL153101 / NHLBI NIH HHS P01 HL084207 / NHLBI NIH HHS T32 HL134643 / NHLBI NIH HHS T32 DK007690 / NIDDK NIH HHS R01 HL134850 / NHLBI NIH HHS I01 BX004249 / BLRD VA
Language: English
Date published: 08/2020
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984070454802771

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