title: Renoprotective effects of anti-TGF-β antibody and antihypertensive therapies in Dahl S rats.
abstract: This study examined the effects of anti-TGF-β antibody (1D11) therapy in Dahl S (S) rats fed a 4% NaCl diet. Baseline renal expression of TGF-β1 and the degree of injury were lower in female than male S rats maintained on a 0.4% NaCl diet. 4% NaCl diet increased mean arterial pressure (MAP), proteinuria, and renal injury to the same extent in both male and female S rats. Chronic treatment with 1D11 had renoprotective effects in both sexes. The ability of 1D11 to oppose the development of proteinuria when given alone or in combination with antihypertensive agents was further studied in 6-wk-old female S rats, since baseline renal injury was less than that seen in male rats. 1D11, diltiazem, and hydrochlorothiazide (HCT) attenuated the development of hypertension, proteinuria, and glomerular injury. 1D11 had no additional effect when given in combination with these antihypertensive agents. We also explored whether 1D11 could reverse renal injury in 9-wk-old male S rats with preexisting renal injury. MAP increased to 197 ± 4 mmHg and proteinuria rose to >300 mg/day after 3 wk on a 4% NaCl diet. Proteinuria was reduced by 30-40% in rats treated with 1D11, HCT, or captopril + 1D11, but the protective effect was lost in rats fed the 4% NaCl diet for 6 wk. Nevertheless, 1D11, HCT, and captopril + 1D11 still reduced renomedullary and cardiac fibrosis. These results indicate that anti-TGF-β antibody therapy reduces renal and cardiac fibrosis and affords additional renoprotection when given in combination with various antihypertensive agents in Dahl S rats.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39211, USA.
authors.forename: Sydney R
authors.initials: SR
authors.lastname: Murphy
authors.forename: Annette J
authors.initials: AJ
authors.lastname: Dahly-Vernon
authors.forename: Kathryn M J
authors.initials: KM
authors.lastname: Dunn
authors.forename: Chun Cheng Andy
authors.initials: CC
authors.lastname: Chen
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ledbetter
authors.forename: Jan M
authors.initials: JM
authors.lastname: Williams
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D004110:Diltiazem / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006852:Hydrochlorothiazide / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D051381:Rats; D020303:Rats, Inbred Dahl; D012727:Sex Characteristics; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000959:Antihypertensive Agents; D017673:Sodium Chloride, Dietary; D016212:Transforming Growth Factor beta; D006852:Hydrochlorothiazide; D002216:Captopril; D004110:Diltiazem