title: Central Renin-Angiotensin System Activation and Inflammation Induced by High-Fat Diet Sensitize Angiotensin II-Elicited Hypertension.
abstract: Obesity has been shown to promote renin-angiotensin system activity and inflammation in the brain and to be accompanied by increased sympathetic activity and blood pressure. Our previous studies demonstrated that administration of a subpressor dose of angiotensin (Ang) II sensitizes subsequent Ang II-elicited hypertension. The present study tested whether high-fat diet (HFD) feeding also sensitizes the Ang II-elicited hypertensive response and whether HFD-induced sensitization is mediated by an increase in renin-angiotensin system activity and inflammatory mechanisms in the brain. HFD did not increase baseline blood pressure, but enhanced the hypertensive response to Ang II compared with a normal-fat diet. The sensitization produced by the HFD was abolished by concomitant central infusions of either a tumor necrosis factor-α synthesis inhibitor, pentoxifylline, an Ang II type 1 receptor blocker, irbesartan, or an inhibitor of microglial activation, minocycline. Furthermore, central pretreatment with tumor necrosis factor-α mimicked the sensitizing action of a central subpressor dose of Ang II, whereas central pentoxifylline or minocycline abolished this Ang II-induced sensitization. Real-time quantitative reverse transcription-polymerase chain reaction analysis of lamina terminalis tissue indicated that HFD feeding, central tumor necrosis factor-α, or a central subpressor dose of Ang II upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines, whereas inhibition of Ang II type 1 receptor and of inflammation reversed these changes. The results suggest that HFD-induced sensitization of Ang II-elicited hypertension is mediated by upregulation of the brain renin-angiotensin system and of central proinflammatory cytokines.
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City. baojian-xue@uiowa.edu.
authors.forename: Baojian
authors.initials: B
authors.lastname: Xue
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Thunhorst
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City.
authors.forename: Terry G
authors.initials: TG
authors.lastname: Beltz
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Felder
authors.affiliation: From the Departments of Psychological and Brain Sciences (B.X., R.L.T., F.G., T.G.B., A.K.J.), Pharmacology (A.K.J.), Internal Medicine (Y.Y., R.B.F.), and the François M. Abboud Cardiovascular Research Center (B.X., R.B.F., A.K.J.), University of Iowa, Iowa City.
authors.forename: Alan Kim
authors.initials: AK
authors.lastname: Johnson
mesh_terms: D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000804:Angiotensin II
keywords: angiotensin II; blood pressure; high-fat diet; proinflammatory cytokine; sensitization