SUN-150 RENAL MICROVASCULAR RAREFACTION PRECEDES THE DEVELOPMENT OF HYPERTENSION AND RENAL DAMAGE IN MICE WITH A LOW NEPHRON ENDOWMENT

Abstract

The a8 integrin chain is a matrix receptor on mesenchymal cells and plays an important role in renal development. a8 integrin-deficient mice (itga8-/-) have a reduced renal mass. Itga8-/- on a C57BL/6 genetic background are normotensive, while itga8-/- on a 129SV background develop hypertension and renal damage. The reduction of renal mass is comparable in both strains. Therefore, hypertension and renal damage are not merely a consequence of low nephron endowment. As hypertension is frequently associated with vascular rarefaction, we studied renal microvascular supply in the kidneys of both itga8-/- strains. Itga8-/- were backcrossed on a C57Bl/6 or on a 129SV background. At the age of 10 and 30 weeks blood pressure was measured by telemetry. At the age of 10 days and 10 weeks the renal microvascular supply was assessed after staining renal tissue with the endothelial cell marker CD31/Pecam. Renal physiological parameters (i.e. albuminuria, serum creatinine and urea) and renal fibrosis (collagen deposition and fibroblast activation) were evaluated. The renal mass of both itga8-/- C57Bl/6 und itga8-/- 129SV was reduced to 50%. Blood pressure was elevated and glomerulosclerosis was detected at the age of 10 weeks in itga8-/- 129SV only. Serum creatinine, serum urea and albuminuria were increased in itga8-/- 129SV, not in itga8-/- C57Bl/6. On the C57Bl/6 background there were no differences in renal capillary numbers of itga8-/- compared to itga8+/+ controls. In contrast, a reduced renal capillary supply was observed in itga8-/- on a 129SV background at the age of 10 weeks. In this strain, a reduced number of renal capillaries was already detected at the age of 10 days, when no overt renal changes could be observed. The development of hypertension in itga8-/- mice with a reduced renal mass is associated with renal microvascular rarefaction. A reduced number of capillaries in the kidney of these mice can be detected as early as at day 10 of life, and might therefore precede the development of hypertension and glomerulosclerosis and contribute to renal damage.