Angiotensin II Augments Renal Vascular Smooth Muscle Soluble GC Expression Via an AT Receptor-forkhead Box Subclass O Transcription Factor Signalling Axis

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2021 May 8

PMID 33963547

Citations 3

Authors

Joseph C Galley

Scott A Hahn

Megan P Miller

Brittany G Durgin

Edwin K Jackson

Sean D Stocker

Adam C Straub

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Reduced renal blood flow triggers activation of the renin-angiotensin-aldosterone system (RAAS) leading to renovascular hypertension. Renal vascular smooth muscle expression of the NO receptor, soluble GC (sGC), modulates the vasodilator response needed to control renal vascular tone and blood flow. Here, we tested if angiotensin II (Ang II) affects sGC expression via an AT receptor-forkhead box subclass O (FoxO) transcription factor dependent mechanism.

Experimental Approach: Using a murine two-kidney-one-clip (2K1C) renovascular hypertension model, we measured renal artery vasodilatory function and sGC expression. Additionally, we conducted cell culture studies using rat renal pre-glomerular smooth muscle cells (RPGSMCs) to test the in vitro mechanistic effects of Ang II treatment on sGC expression and downstream function.

Key Results: Contralateral, unclipped renal arteries in 2K1C mice showed increased NO-dependent vasorelaxation compared to sham control mice. Immunofluorescence studies revealed increased sGC protein expression in 2K1C contralateral renal arteries over sham controls. RPGSMCs treated with Ang II caused a significant up-regulation of sGC mRNA and protein expression as well as downstream sGC-dependent signalling. Ang II signalling effects on sGC expression occurred through an AT receptor and FoxO transcription factor-dependent mechanism at both the mRNA and protein expression levels.

Conclusion And Implications: Renal artery smooth muscle, in vivo and in vitro, up-regulates expression of sGC following RAAS activity. In both cases, up-regulation of sGC leads to increased downstream cGMP signalling, suggesting a previously unrecognized protective mechanism to improve renal blood flow in the uninjured contralateral renal artery.

Linked Articles: This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc.

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References

Benjamin M, Fazel P, Filardo G, Choi J, Stoler R . Prevalence of and risk factors of renal artery stenosis in patients with resistant hypertension. Am J Cardiol. 2013; 113(4):687-90. DOI: 10.1016/j.amjcard.2013.10.046. View

Salminen A, Kaarniranta K, Kauppinen A . Crosstalk between Oxidative Stress and SIRT1: Impact on the Aging Process. Int J Mol Sci. 2013; 14(2):3834-59. PMC: 3588074. DOI: 10.3390/ijms14023834. View

Harrison-Bernard L, Navar L, Ho M, Vinson G, El-Dahr S . Immunohistochemical localization of ANG II AT1 receptor in adult rat kidney using a monoclonal antibody. Am J Physiol. 1997; 273(1 Pt 2):F170-7. DOI: 10.1152/ajprenal.1997.273.1.F170. View

Majid D, Navar L . Nitric oxide in the mediation of pressure natriuresis. Clin Exp Pharmacol Physiol. 1997; 24(8):595-9. DOI: 10.1111/j.1440-1681.1997.tb02098.x. View

Motta M, Divecha N, Lemieux M, Kamel C, Chen D, Gu W . Mammalian SIRT1 represses forkhead transcription factors. Cell. 2004; 116(4):551-63. DOI: 10.1016/s0092-8674(04)00126-6. View

Rippe C, Zhu B, Krawczyk K, van Bavel E, Albinsson S, Sjolund J . Hypertension reduces soluble guanylyl cyclase expression in the mouse aorta via the Notch signaling pathway. Sci Rep. 2017; 7(1):1334. PMC: 5430981. DOI: 10.1038/s41598-017-01392-1. View

Derkx F, SCHALEKAMP M . Renal artery stenosis and hypertension. Lancet. 1994; 344(8917):237-9. DOI: 10.1016/s0140-6736(94)93002-3. View

Rahaman M, Nguyen A, Miller M, Hahn S, Sparacino-Watkins C, Jobbagy S . Cytochrome b5 Reductase 3 Modulates Soluble Guanylate Cyclase Redox State and cGMP Signaling. Circ Res. 2017; 121(2):137-148. PMC: 5527687. DOI: 10.1161/CIRCRESAHA.117.310705. View

Doughan A, Harrison D, Dikalov S . Molecular mechanisms of angiotensin II-mediated mitochondrial dysfunction: linking mitochondrial oxidative damage and vascular endothelial dysfunction. Circ Res. 2007; 102(4):488-96. DOI: 10.1161/CIRCRESAHA.107.162800. View

10.

DeLalio L, Hahn S, Katayama P, Wenner M, Farquhar W, Straub A . Excessive dietary salt promotes aortic stiffness in murine renovascular hypertension. Am J Physiol Heart Circ Physiol. 2020; 318(5):H1346-H1355. PMC: 7346535. DOI: 10.1152/ajpheart.00601.2019. View

11.

Kalra P, Guo H, Kausz A, Gilbertson D, Liu J, Chen S . Atherosclerotic renovascular disease in United States patients aged 67 years or older: risk factors, revascularization, and prognosis. Kidney Int. 2005; 68(1):293-301. DOI: 10.1111/j.1523-1755.2005.00406.x. View

12.

Sandner P, Stasch J . Anti-fibrotic effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence. Respir Med. 2017; 122 Suppl 1:S1-S9. DOI: 10.1016/j.rmed.2016.08.022. View

13.

Granger J, Alexander B, Llinas M . Mechanisms of pressure natriuresis. Curr Hypertens Rep. 2002; 4(2):152-9. DOI: 10.1007/s11906-002-0040-3. View

14.

van der Horst A, Tertoolen L, de Vries-Smits L, Frye R, Medema R, Burgering B . FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1). J Biol Chem. 2004; 279(28):28873-9. DOI: 10.1074/jbc.M401138200. View

15.

Iglesias J, HAMBURGER R, Feldman L, Kaufman J . The natural history of incidental renal artery stenosis in patients with aortoiliac vascular disease. Am J Med. 2000; 109(8):642-7. DOI: 10.1016/s0002-9343(00)00605-7. View

16.

Crassous P, Couloubaly S, Huang C, Zhou Z, Baskaran P, Kim D . Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model. Am J Physiol Heart Circ Physiol. 2012; 303(5):H597-604. PMC: 3468472. DOI: 10.1152/ajpheart.00138.2012. View

17.

Ichiki T, Tokunou T, Fukuyama K, Iino N, Masuda S, Takeshita A . Cyclic AMP response element-binding protein mediates reactive oxygen species-induced c-fos expression. Hypertension. 2003; 42(2):177-83. DOI: 10.1161/01.HYP.0000079791.26014.04. View

18.

Biggs 3rd W, Meisenhelder J, Hunter T, Cavenee W, Arden K . Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci U S A. 1999; 96(13):7421-6. PMC: 22101. DOI: 10.1073/pnas.96.13.7421. View

19.

OConnor P, Cowley Jr A . Modulation of pressure-natriuresis by renal medullary reactive oxygen species and nitric oxide. Curr Hypertens Rep. 2010; 12(2):86-92. PMC: 3722865. DOI: 10.1007/s11906-010-0094-6. View

20.

Murphy W, Coleman T, Smith T, Stanek K . Effects of graded renal artery constriction on blood pressure, renal artery pressure, and plasma renin activity in Goldblatt hypertension. Hypertension. 1984; 6(1):68-74. DOI: 10.1161/01.hyp.6.1.68. View