Pressor response to angiotensin II is enhanced in aged mice and associated with inflammation, vasoconstriction and oxidative stress

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-1 beta, 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.