Advanced atherosclerosis is associated with inflammation, vascular dysfunction and oxidative stress, but not hypertension

Although hypertension may involve underlying inflammation, it is unknown whether advanced atherosclerosis - a chronic inflammatory condition - can by itself promote hypertension. We thus tested if advanced atherosclerosis in chronically hypercholesterolemic mice is associated with systemic and end-organ inflammation, vascular dysfunction and oxidative stress, and whether blood pressure is higher than in control mice. Male ApoE^-/- and wild-type (C57Bl6J) mice were placed on a high fat or chow diet, respectively, from 5 to 61 weeks of age. Expression of several cytokines (including IL-6, TNF-α, IFN-γ and/or IL-1β) was elevated in plasma, brain, and aorta of ApoE^-/- mice. Aortic superoxide production was ∼3.5-fold greater, and endothelium-dependent relaxation was markedly reduced in aorta and mesenteric artery of ApoE^-/- versus wild-type mice. There was no difference in blood pressure of aged ApoE^-/- (104±3mmHg, n=13) and wild-type mice (113±1mmHg, n=18). To clarify any effects of aging alone, findings from 61 week-old wild-type mice were compared with those from young (8-12 weeks old) chow-fed wild-type mice. The data indicate that aging alone increased renal and aortic expression of numerous cytokines (including CCL2, CCL7 and IL-1β). Aging had no effect on blood pressure, systemic inflammation, oxidative stress or endothelial function. Despite systemic and end-organ inflammation, oxidative stress and endothelial dysfunction, advanced atherosclerosis does not necessarily result in elevated blood pressure.