title: Sustained renal interstitial macrophage infiltration following chronic angiotensin II infusions.
abstract: Chronic angiotensin (ANG) II infusions into rats lead to augmented intrarenal levels of ANG II and inflammatory factors, impaired renal function, and progressive hypertension. Residual effects persist after cessation of ANG II infusions, as manifested by a hypertensive response to high-salt intake. This study was performed to determine the residual cytokines and chemokines following the cessation of ANG II infusion. Male Sprague-Dawley rats, maintained on a normal diet, received either a sham operation or continuous ANG II infusion (120 ng/min) subcutaneously via minipumps. The ANG II-infused rats were further subdivided into three subgroups. Minipumps were removed on day 12 with subsequent harvesting of kidneys at 0, 3, and 6 days after cessation of ANG II infusion. After 12 days of ANG II infusion, systolic blood pressure, interstitial fibrosis, preglomerular hypertrophy, and interstitial macrophage infiltration were significantly enhanced compared with the shams. By 3 days following the cessation of ANG II infusion, systolic blood pressure was normalized; however, interstitial fibrosis and preglomerular hypertrophy were still present. Furthermore, increased interstitial macrophage infiltration was still present 6 days after cessation of ANG II infusion. Importantly, augmented mRNA levels of monocyte chemotactic protein (MCP)-1 (1.55 +/- 0.15 vs. 1.00 +/- 0.13, relative ratio) and transforming growth factor (TGF)-beta(1) (1.52 +/- 0.16 vs. 1.00 +/- 0.08) persisted 6 days after the withdrawal of ANG II infusion (1.60 +/- 0.20 for MCP-1 and 1.43 +/- 0.17 for TGF-beta(1)). Thus, the ANG II-induced activation of MCP-1 and TGF-beta(1) is sustained and may account for the persistent effect of chronic ANG II infusions on interstitial macrophage infiltration, suggesting a possible mechanism for the development of salt sensitivity in ANG II-dependent hypertension.
authors.affiliation: Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, Louisiana 70112-2699, USA.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
authors.forename: Yuki
authors.initials: Y
authors.lastname: Suzaki
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000808:Angiotensinogen / Q000096:biosynthesis; D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000502:physiology; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000808:Angiotensinogen; D000804:Angiotensin II; D020780:Matrix Metalloproteinase 9