title: Renal inflammatory markers during the onset of hypertension in spontaneously hypertensive rats.
abstract: Early blockade of the renin-angiotensin system is successful in delaying the development of hypertension in spontaneously hypertensive rats (SHRs) and ameliorating organ damage by inhibition of the inflammatory response. In this study, we investigated the role of the angiotensin II type 1 receptor (AT1R) in the early renal inflammatory response in SHR. Blood pressure development and renal inflammatory markers were measured in 4-, 8- and 12-week-old SHR and age-matched Wistar Kyoto (WKY) rats. Separate groups of SHRs were transiently treated with the AT1R blocker losartan between 4 and 8 weeks of age. Urinary excretion of the renal injury markers osteopontin and neutrophil gelatinase-associated lipocalin increased in young SHR. Further, renal expression of inflammatory genes was also increased in young SHR. Losartan inhibited the increase of these inflammatory markers. In contrast, gene expression of the renal injury marker and T-cell inducer kidney injury molecule-1 (KIM-1) was reduced in 4-week-old SHR when compared with WKY. Similarly, the T-cell marker CD3 was significantly decreased in 4-week-old SHR. These effects were not antagonized by AT1R blockade. This study confirms the presence of an early renal inflammatory response in SHR that can be blocked by AT1R antagonism. In addition, it demonstrates that KIM-1 does not behave as a pure kidney injury marker in young SHR, but may reflect kidney maturation.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Bart Fj
authors.initials: BF
authors.lastname: Heijnen
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Helma
authors.initials: H
authors.lastname: Van Essen
authors.affiliation: 1] Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands [2] Department of Internal Medicine, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ben Ja
authors.initials: BJ
authors.lastname: Janssen
authors.affiliation: Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
authors.forename: Harry Aj
authors.initials: HA
authors.lastname: Struijker-Boudier
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism* / Q000652:urine; D017252:CD3 Complex / Q000378:metabolism; D015870:Gene Expression; D006439:Hemodynamics / Q000502:physiology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D016133:Polymerase Chain Reaction; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000096:biosynthesis / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology; D000097382:CD68 Molecule
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D017252:CD3 Complex; D019808:Losartan; D012313:RNA; D044140:Receptor, Angiotensin, Type 1; C067980:CD68 antigen, human; D000097382:CD68 Molecule