Endothelium-mediated regulation of renin secretion

Abstract

The aim of the present study was to investigate the endothelial influence on renin secretion of isolated juxtaglomerular cells. Specifically the role of nitric oxide (NO) and of endothelin was studied. Coculture of primary cultures of juxtaglomerular cells with aortic and microvascular endothelial cells decreased renin secretion. Inhibition of NO formation by absence of l-arginine or presence of N omega-nitro-l-arginine caused a marked decrease in cGMP accumulation and a reduction in renin secretion in cocultures. Exogenous NO (NO liberators sodium nitroprusside/SIN 1) stimulated the 20-hour renin secretion from juxtaglomerular cells markedly, too. The effect of NO on renin secretion was biphasic: short-time inhibition and long-time stimulation of renin release. NO's stimulatory effect on renin secretion is dependent on extracellular calcium, but independent on cAMP or cGMP accumulation. Endothelin 1, 2, and 3 did not affect basal renin secretion, but inhibited cAMP stimulated renin release to a similar extent. Endothelin's action is not mediated via the subtype A endothelin receptor, but seems to involve calcium mobilization in juxtaglomerular cells that is dependent on extracellular calcium and associated with prominent calcium activated chloride channels. Taken together, coculture of juxtaglomerular cells with endothelial cells inhibits renin secretion despite the stimulatory effect of native NO released from endothelial cells. cAMP stimulated renin secretion is inhibited by all three endothelin isoforms thus contributing to the inhibition of renin secretion in coculture.

Vascular endothelium and nitric oxide in childhood hypertension

“…In vitro, however, in renal cortical slices, L-NMMA increases [117,118] and NO decreases [110] renin secretion. This is perhaps partly explained by the biphasic effect of NO on renin secretion: a short-term inhibition and a long-term stimulation [116]. Conversely, in isolated juxtaglomerular cells renin secretion is increased by NO and decreased by NOS inhibitors.…”

“…Furthermore NO inhibition attenuates the renin response to a low-salt diet [109] and pressure-dependent renin release [112], suggesting a necessity for NO to be present for the normal renin response to salt depletion and low blood pressure. In studies using cultured juxta glomerular cells, NO appears to stimulate renin release [113][114][115] and this is dependent on extracellular Ca 2+ [116]. In vitro, however, in renal cortical slices, L-NMMA increases [117,118] and NO decreases [110] renin secretion.…”

Physiology of Kidney Renin

“…Specifically, the expression of eNOS in the afferent arteriole has been shown for a number of mammalian species (40, 41, 896). A coculture of JG cells with endothelial cells revealed both inhibitory and stimulatory signaling derived from the endothelial cells, with the stimulatory component related to endothelium-dependent NO formation (462,481,773). In contrast, the NOS inhibition in the absence of endothelial cells had no effect on the renin secretion from JG cells, presumably due to the lack of NOS expression in JG cells (773).…”

Endothelial damage in white coat hypertension: role of lectin-like oxidized low-density lipoprotein-1

“…Additionally, some studies report that NOx lowers plasma renin levels; however, other studies have shown that NOx increases renin levels. 35,36 Although the mechanism of this impairment is not well understood, a number of studies have shown that the eNOS pathway and/or the released NOx are influenced by oxLDL. 37 As previous results are controversial, further studies are needed to determine the cellular and molecular mechanisms by which NOx regulates various precursors to HT.…”