Expression of endothelial nitric oxide synthase in developing rat kidney

Abstract

Endothelium-derived nitric oxide (NO) is synthesized within the developing kidney and may play a crucial role in the regulation of renal hemodynamics. The purpose of this study was to establish the expression and intrarenal localization of the NO-synthesizing enzyme endothelial NO synthase (eNOS) during kidney development. Rat kidneys from 14 (E14)-, 16 (E16)-, 18 (E18)-, and 20-day-old (E20) fetuses and 1 (P1)-, 3 (P3)-, 7 (P7)-, 14 (P14)-, and 21-day-old (P21) pups were processed for immunocytochemical and immunoblot analysis. In fetal kidneys, expression of eNOS was first observed in the endothelial cells of the undifferentiated intrarenal capillary network at E14. At E16, strong eNOS immunoreactivity was observed in the endothelial cells of renal vesicles, S-shaped bodies (stage II glomeruli), and stage III glomeruli at the corticomedullary junction. At E18-20, early-stage developing glomeruli located in the subcapsular region showed less strong eNOS immunoreactivity than those of E16. The eNOS-positive immature glomeruli were observed in the nephrogenic zone until 7 days after birth. In fetal kidneys, eNOS was also expressed in the medulla in the endothelial cells of the capillaries surrounding medullary collecting ducts. After birth, eNOS immunostaining gradually increased in the developing vascular bundles and peritubular capillaries in the medulla and was highest at P21. Surprisingly, eNOS was also expressed in proximal tubules, in the endocytic vacuolar apparatus, only at P1. The strong expression of eNOS in the early stages of developing glomeruli and vasculature suggests that eNOS may play a role in regulating renal hemodynamics of the immature kidney.

Effect of combining an ACE inhibitor and a VDR activator on glomerulosclerosis, proteinuria, and renal oxidative stress in uremic rats

“…In both cases, iNOS inhibition was associated with a significant improvement in glomerular filtration rate. eNOS is expressed in endothelial cells, including those of the kidney, consistent with its important role in maintaining endothelial function (16). Our data show that eNOS is markedly suppressed in untreated uremic rats.…”

Lack of Endothelial Nitric-Oxide Synthase Leads to Progressive Focal Renal Injury

“…A recent study of postnatal rat kidney 4 found eNOS staining in endothelial cells beginning at embryonic day 14 and maintaining a blood vessel-associated location from that time forward. In addition, eNOS appears in proximal tubule epithelial cells, but only at postnatal day 1, when it is concentrated within lysosomes and endocytic vacuoles.…”

“…In addition, eNOS appears in proximal tubule epithelial cells, but only at postnatal day 1, when it is concentrated within lysosomes and endocytic vacuoles. 4 The authors suggest that this eNOS has been scavenged from glomerular filtrate and report that no immunoreactive eNOS was present in the tubules following that single day of appearance. 4 Although we have, in this communication, reported a nonvascular expression of eNOS in postnatal mouse proximal tubules, our observations vary substantially from those of Han et al 4 Rather than a discrete zone of staining in mouse epithelial cells, which would be expected if the enzyme were located in phagocytic vacu- Figure 5.…”

“…3 As its name implies, eNOS is located within the renal vascular endothelium in the adult. However, recent findings indicate that, in neonatal rats, this enzyme is also transiently present in proximal tubules, 4 whereas eNOS mRNA is present in the inner medullary collecting duct in the adult. 5 The renal anatomy of eNOS knockout mice has been previously reported to be normal in appearance.…”

Neuronal nitric oxide synthase, nNOS, regulates renal hemodynamics in the postnatal developing piglet

“…Various laboratories have identified eNOS throughout the adult kidney including abundant expression in the renal vasculature, and functional studies have demonstrated eNOS as the major isoform that provides NO vasorelaxation within the adult kidney (12,13,(30)(31)(32). Although various groups have identified nNOS within the adult's pre-and postglomerular resistance vessels and tubules, the greatest localization of nNOS occurs in the macula densa of the adult kidney, where it plays a critical role in the tubuloglomerular feedback mechanism (12,13,31,32).…”