Differential connexin expression in preglomerular and postglomerular vasculature: accentuation during diabetes

Gap junctions may play an important role in regulating renal blood flow and glomerular responses. We have therefore made a comprehensive analysis of connexin expression in the renal vasculature of control and diabetic mice since elevated glucose has been reported to down-regulate connexin 43 in vascular cells in vitro.

Connexin distribution was determined with immunohistochemistry using subtype-specific and cell type-specific antibodies. Diabetes was induced with streptozotocin (120/80 mg/kg, intraperitoneally) in C57BL/6 mice.

Connexins 37, 40, and 43 were expressed in endothelial cells of the renal, lobar, arcuate, and interlobular arteries and afferent arterioles, although connexin 43 was weak in the renal and arcuate arteries. Connexin 37 was detected in the media of arcuate, interlobular arteries and afferent arterioles and connexins 37 and 40 were found in renin-secreting cells. Both connexins 37 and 40 were expressed in extraglomerular mesangial cells, connexin 40 was abundantly expressed in intraglomerular mesangial cells, but connexin 37 was limited to mesangial cells at the vascular pole. In contrast, only connexin 43 was detected in endothelial cells of efferent arterioles and there was no connexin staining in the media. In diabetes, connexin 40 was expressed in smooth muscle cells along afferent arterioles, glomerular connexin staining was more extensive and connexin 43 was detected in renin-secreting cells. In contrast connexin 43 expression in endothelial cells of efferent arterioles was markedly reduced.

The renal vasculature and mesangial cells are well coupled on the preglomerular side but there is little evidence that the coupling extends into the efferent arteriole. This pattern of cell coupling is accentuated during diabetes.