Influence of carnosine and carnosinase-1 on diabetes-induced afferent arteriole vasodilation: implications for glomerular hemodynamics

Dysregulation in glomerular hemodynamics favors hyperfiltration in diabetic kidney disease (DKD). Although carnosine supplementation ameliorates features of DKD, its effect on glomerular vasoregulation is not known. We assessed the influence of carnosine and carnosinase-1 (CN1) on afferent glomerular arteriole vasodilation and its association with glomerular size, hypertrophy and nephrin expression in diabetic BTBR mice. Two cohorts of mice including appropriate controls were studied i.e., diabetic mice receiving oral carnosine supplementation (cohort 1) and human CN1 (hCN1) transgenic (TG) diabetic mice (cohort 2). Lumen area ratio (LAR) of the afferent arterioles and glomerular parameters were measured by conventional histology. Three-dimensional analysis using a tissue clearing strategy was also employed. In both cohorts, LAR was significantly larger in diabetic BTBR vs non-diabetic BTBR mice (0.41±0.05 vs 0.26±0.07; p