Antihypertensive effects of chronic anti-TGF-β antibody therapy in Dahl S rats

This study examined the role of transforming growth factor-β (TGF-β) in the development of hypertension and renal disease in 9-wk-old male Dahl salt-sensitive (Dahl S) rats fed an 8% NaCl diet for 3 wk. The rats received an intraperitoneal injection of a control or an anti-TGF-β antibody (anti-TGF-β Ab) every other day for 2 wk. Mean arterial pressure was significantly lower in Dahl S rats treated with anti-TGF-β Ab (177 ± 3 mmHg, n = 12) than in control rats (190 ± 4 mmHg, n = 17). Anti-TGF-β Ab therapy also reduced proteinuria from 226 ± 20 to 154 ± 16 mg/day. Renal blood flow, cortical blood flow, and creatinine clearance were not significantly different in control and treated rats; however, medullary blood flow was threefold higher in the treated rats than in the controls. Despite the reduction in proteinuria, the degree of glomerulosclerosis and renal hypertrophy was similar in control and anti-TGF-β Ab-treated rats. Renal levels of TGF-β1 and -β2, α-actin, type III collagen, and fibronectin mRNA decreased in rats treated with anti-TGF-β Ab. To examine whether an earlier intervention with anti-TGF-β Ab would confer additional renoprotection, these studies were repeated in a group of 6-wk-old Dahl S rats. Anti-TGF-β Ab therapy significantly reduced blood pressure, proteinuria, and the degree of glomerulosclerosis and renal medullary fibrosis in this group of rats. The results indicate that anti-TGF-β Ab therapy reduces blood pressure, proteinuria, and the renal injury associated with hypertension.