Faculty Collaboration Database

Increased Susceptibility of Mice Lacking Renin-b to Angiotensin II-Induced Organ Damage. Hypertension 2020 Aug;76(2):468-477

Date

06/09/2020

Pubmed ID

32507043

Pubmed Central ID

PMC7347438

DOI

10.1161/HYPERTENSIONAHA.120.14972

Scopus ID

2-s2.0-85087872461 (requires institutional sign-in at Scopus site)   8 Citations

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^Null 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^Null 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^Null to the same degree. Although the blood pressure between Ren-b^Null and wild-type mice was elevated equally, 4-week infusion of Ang II resulted in exacerbated cardiac remodeling in Ren-b^Null mice compared with wild type. Ren-b^Null 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.

Author List

Nakagawa P, Nair AR, Agbor LN, Gomez J, Wu J, Zhang SY, Lu KT, Morgan DA, Rahmouni K, Grobe JL, Sigmund CD

Authors

Justin L. Grobe PhD Professor in the Physiology department at Medical College of Wisconsin
Pablo Nakagawa PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensin II
Animals
Blood Pressure
Genetic Predisposition to Disease
Hypertension
Kidney
Male
Mice
Mice, Knockout
Protein Isoforms
Renin
Renin-Angiotensin System