Research Paper Volume 9, Issue 6 pp 1595—1606
Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress
- 1 Cardiovascular Disease Program, Biomedicine Discovery Institute, Department of Pharmacology, Monash University, Victoria, Australia
- 2 Department of Surgery, Monash Medical Centre, Southern Clinical School, Monash University, Victoria, Australia
- 3 The Institute for Molecular Bioscience, The University of Queensland, Queensland, Australia
- 4 Current affiliation: Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Victoria, Australia
- 5 Current affiliation: Department of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern University, Ohio, USA
- 6 Hudson Institute of Medical Research, Victoria, Australia
received: April 17, 2017 ; accepted: June 20, 2017 ; published: June 28, 2017 ;https://doi.org/10.18632/aging.101255
How to Cite
Copyright: Dinh et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.