English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
 
 
DownloadE-Mail
  Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signalling

Wirth, A., Wang, S., Takefuji, M., Tang, C., Althoff, T. F., Schweda, F., et al. (2016). Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signalling. CARDIOVASCULAR RESEARCH, 109(1), 131-140. doi:10.1093/cvr/cvv249.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Wirth, Angela1, Author              
Wang, ShengPeng1, Author              
Takefuji, Mikito1, Author              
Tang, Cong1, Author              
Althoff, Till F.1, Author              
Schweda, Frank, Author
Wettschureck, Nina1, Author              
Offermanns, Stefan1, Author              
Affiliations:
1Pharmacology, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591696              

Content

show
hide
Free keywords: ENDOTHELIAL DYSFUNCTION; ANGIOTENSIN-II; GLOBAL BURDEN; NITRIC-OXIDE; HYPERTENSION; DISEASE; ACTIVATION; MECHANISMS; KIDNEY; HEARTCardiovascular System & Cardiology; Ageing; Blood pressure; Endothelin; Hypertension; Smooth muscle;
 Abstract: Aims Arterial hypertension is a major risk factor for cardiovascular diseases. The kidney and its natriuretic function are in the centre of the prevailing models to explain the pathogenesis of hypertension; however, the mechanisms underlying blood pressure elevation remain unclear in most patients. Development of hypertension is strongly correlated with age, and this blood pressure increase typically accelerates in the fourth decade of life. The cause of age-dependent blood pressure elevation is poorly understood. This study aims to understand the role of procontractile G-protein-mediated signalling pathways in vascular smooth muscle in age-dependent hypertension. Methods and results Similar to humans at mid-life, we observed in 1-year-old mice elevated blood pressure levels without any evidence for increased vessel stiffness, impaired renal function, or endocrine abnormalities. Hypertensive aged mice showed signs of endothelial dysfunction and had an increased vascular formation of reactive oxygen species (ROS) and elevated endothelial ET-1 expression. Age-dependent hypertension could be normalized by ETA receptor blockade, smooth muscle-specific inactivation of the gene encoding the ETA receptor, as well as by acute disruption of downstream signalling via induction of smooth muscle-specific G alpha(12)/G alpha(13), G alpha(q)/G alpha(11), or LARG deficiency using tamoxifen-inducible smooth muscle-specific conditional mouse knock-out models. Induction of smooth muscle-specific ETA receptor deficiency normalized the blood pressure in aged mice despite the continuous presence of signs of endothelial dysfunction. Conclusion Age-dependent blood pressure elevation is due to a highly reversible activation of procontractile signalling in vascular smooth muscle cells indicating that increased vascular tone can be a primary factor in the development of hypertension.

Details

show
hide
Language(s): eng - English
 Dates: 2016
 Publication Status: Published in print
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000368414600014
DOI: 10.1093/cvr/cvv249
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CARDIOVASCULAR RESEARCH
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND : OXFORD UNIV PRESS
Pages: - Volume / Issue: 109 (1) Sequence Number: - Start / End Page: 131 - 140 Identifier: ISSN: 0008-6363