Figure 5.

Endothelin A receptor blockade prevents mesangial process invasion of glomerular capillaries and ameliorates GBM damage in Alport mice. 129 Sv Alport animals were treated with the endothelin A receptor specific blocking agent Sitaxentan from 2 weeks to 7 weeks of age. Dual staining demonstrates absence of integrin α8 immunostaining in the glomerular capillaries, which are dual stained with anti-laminin α5 antibodies (Panel A). Arrows denote integrin α8 immunopositivity in the capillary loops of the glomeruli from untreated 129 Sv Autosomal Alport mice and C57 Bl/6 X-linked Alport mice, and the relative absence of integrin α8 immunopositivity in the sitaxentan-treated mice. Sitaxentan ameliorates GBM dysmorphology and (Panel B), largely normalizing the irregular thickening and thinning observed for the GBM of 7 week old Alport mice. Bar=500nm. Sitaxentan treatment does not affect blood pressure (Panel C). Wild type and Alport mice were treated with nothing (control), vehicle (CMC), ramipril (positive control for an agent known to effect blood pressure), or sitaxentan for 1 week and blood pressures measured (5 measures per condition) using a tail cuff method (CODA 2). While blood pressure was lower in the ramipril-treated mice, sitaxentan treatment had no effect on blood pressure.