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.101255How to Cite
Abstract
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.