Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney

Abstract

(WK) S U M M A R Y The endothelin (ET) receptor system is markedly involved in the regulation of renal function under both physiological and pathophysiological conditions. The present study determined the detailed cellular localization of both ET receptor subtypes, ET A and ET B , in the vascular and tubular system of the rat kidney by immunofluorescence microscopy. In the vascular system we observed both ET A and ET B receptors in the media of interlobular arteries and afferent and efferent arterioles. In interlobar and arcuate arteries, only ET A receptors were present on vascular smooth muscle cells. ET B receptor immunoreactivity was sparse on endothelial cells of renal arteries, whereas there was strong labeling of peritubular and glomerular capillaries as well as vasa recta endothelium. ET A receptors were evident on glomerular mesangial cells and pericytes of descending vasa recta bundles. In the renal tubular system, ET B receptors were located in epithelial cells of proximal tubules and inner medullary collecting ducts, whereas ET A receptors were found in distal tubules and cortical collecting ducts. Distribution of ET A and ET B receptors in the vascular and tubular system of the rat kidney reported in the present study supports the concept that both ET receptor subtypes cooperate in mediating renal cortical vasoconstriction but exert differential and partially antagonistic effects on renal medullary function.

Direct Action of Endothelin-1 on Podocytes Promotes Diabetic Glomerulosclerosis

“…16 ETBR expression in podocytes was indeed described by immunoelectron microscopy that allowed visualization of intense immunodeposits indicating ETBR in fully differentiated rat podocytes in situ, particularly in their foot processes. 16 Other researchers found immunoreactive ETAR and ETBR in mesangial and glomerular capillary cells, respectively 17 ; variable staining for immunoreactive ETBR in glomeruli (in parietal epithelial cells and podocytes) has been reported in kidney biopsies from healthy controls and from patients with IgA nephropathy, 14 confirming the findings reported by Karet et al 15 Here we detected ETAR and ETBR expression in primary podocytes, along with novel functional data. ET-1 stimulates calcium transients in podocytes in an ETAR-as well as ETBR-dependent fashion.…”

“…[11][12][13] Both receptors are present in the kidney. [14][15][16][17] It was early recognized that ET-1 displays proliferative effects on mesangial cells that are mediated by ETAR. 18,19 At the glomerular level, ET-1 promotes mesangial cell proliferation, sclerosis, and podocyte injury, although it is not demonstrated whether this latter effect is direct.…”

Renal medullary ETBreceptors produce diuresis and natriuresis via NOS1

“…sodium excretion; nitric oxide synthase 1; guanosine 3Ј,5Ј-cyclic monophosphate; protein kinase G ENDOTHELIN-1 (ET-1), originally described as being released from vascular endothelial cells (46), is now known to be produced by many cell types and exerts a variety of biological effects in various organ systems (27). The renal medulla is a major site of ET-1 synthesis in the body (14,42). Considerable evidence has accumulated in recent years to demonstrate the physiological importance of renal medullary ET-1 in the control of arterial pressure and salt sensitivity.…”

Endothelin A receptor-like immunoreactivity on the basal infoldings of rat renal tubules and collecting ducts

“…However, recent fi ndings on the distribution of the ETA receptor are highly confl icting. For example, one immunohistochemical study reported the presence of the ETA receptor in the renal tubules and collecting ducts (Wendel et al, 2006), whereas another did not (Kuc and Dapenport, 2004). Moreover, an association of the ETA receptor with collecting duct functions was suggested from observations made using mice with a knockout of the collecting duct-specifi c ETA receptor (Ge et al, 2005).…”