Abstract P106: The Role of Inflammasomes and Angiotensin II Type 1 Receptor in the Pressor Responses of Aged Mice to Angiotensin II
Introduction: The prevalence of hypertension increases with age. Chronic low-grade inflammation commonly occurs with ageing, and inflammasomes are important initiators of inflammatory responses. We tested whether aged mice have enhanced pressor responses to angiotensin II (Ang II) and whether this is associated with exaggerated pro-inflammatory and vascular contractile responses. We also tested whether MCC950, a NLRP3 inflammasome inhibitor, reduces blood pressure (BP) in Ang II-treated aged mice.
Methods: Young (8-12 weeks) and aged (24-30 months) male C57Bl6 mice were left untreated, or either treated with vehicle or a slow-pressor dose of Ang II (0.28 mg/kg/day) for 28 days. Another group of aged mice were treated with either Ang II + saline or Ang II + MCC950 (10 mg/kg/day) for 10 days. We measured systolic BP, mRNA expression of inflammatory markers and components of the renin-angiotensin system, and vascular contractile responses.
Results: In young mice, Ang II caused a gradual increase in BP (final BP: 141.6 ± 8.3 mmHg), whereas BP increased by ~20 mmHg from baseline in aged mice, and continued to increase for 28 days (final BP: 155 ± 12.4 mmHg) (n=8-9, P<0.05). Ageing alone increased renal expression of AT1a receptors, NLRP3, Caspase-1, IL-1β, IL-33, CCR2, CCL7 and CCL8 by at least 1.5-fold (n=7-8, all P<0.05). Maximum contractile responses of mesenteric artery were 1.8-fold greater to Ang II and 1.2-fold greater to phenylephrine in aged vs young mice (n=4, both P<0.05). BP was not different between Ang II + saline-treated aged mice (BP: 138.8 ± 6.8 mmHg) and Ang II + MCC950-treated aged mice (BP: 144.7 ± 9.6 mmHg) (n=6-7, P>0.05).
Conclusions: Aged mice have enhanced pressor responses to Ang II and this is associated with exacerbated pro-inflammatory and vascular contractile responses. The NLRP3 inflammasome does not appear to contribute to Ang II-induced hypertension in aged mice.
Author Disclosures: Q.N. Dinh: None. G.R. Drummond: None. B.K. Kemp-Harper: None. H. Diep: None. A.A.B. Robertson: None. M.A. Cooper: None. C.G. Sobey: None. S. Chrissobolis: None.
- © 2015 by American Heart Association, Inc.