Wirth, Angela and Wang, Shengpeng and Takefuji, Mikito and Tang, Cong and Althoff, Till F. and Schweda, Frank and Wettschureck, Nina and Offermanns, Stefan (2016) Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signalling. CARDIOVASCULAR RESEARCH, 109 (1). pp. 131-140. ISSN 0008-6363, 1755-3245
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL DYSFUNCTION; ANGIOTENSIN-II; GLOBAL BURDEN; NITRIC-OXIDE; HYPERTENSION; DISEASE; ACTIVATION; MECHANISMS; KIDNEY; HEART; Ageing; Blood pressure; Endothelin; Hypertension; Smooth muscle |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Mar 2019 12:36 |
| Last Modified: | 07 Mar 2019 09:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2211 |
Actions (login required)
 |
View Item |
