Regulation of cortical collecting duct function: Effect of endothelin

Kurokawa, Kiyoshi; Yoshitomi, Kuniaki; Ikeda, Masahiro; Uchida, Shunya; Naruse, Masahiro; Imai, Masashi

doi:10.1016/0002-8703(93)90207-p

Cited by 33 publications

(27 citation statements)

References 21 publications

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“…In isolated perfused cortical CD, ET-1 inhibition of NaCl reabsorption is dependent on PKC activation and increases in intracellular Ca 2ϩ concentration (31,32,46). ET-1 reduction of Na reabsorption may involve Ca 2ϩ entry through dihydropyridine-type Ca 2ϩ channels associated with a sustained rise in intracellular Ca 2ϩ concentration (30,34).…”

Section: Discussionmentioning

confidence: 99%

“…Fourth, in vitro studies indicate that ET-1 inhibits CD Na transport. ET-1 decreases Na reabsorption by the isolated CD, an effect that may be mediated by inhibition of amiloride-sensitive sodium channel activity (14,31,32,46) and/or Na-K-ATPase activity (53). Perhaps the most compelling evidence implicating CD-derived ET-1 in the regulation of renal Na excretion and BP comes from gene targeting studies.…”

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confidence: 99%

“…of amiloride-sensitive sodium channel activity (14,31,32,46) and/or Na-K-ATPase activity (53). Perhaps the most compelling evidence implicating CD-derived ET-1 in the regulation of renal Na excretion and BP comes from gene targeting studies.…”

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confidence: 99%

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Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

Ge¹,

Bagnall²,

Stricklett³

et al. 2006

American Journal of Physiology-Renal Physiology

190

152

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. Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol Renal Physiol 291: F1274 -F1280, 2006. First published July 25, 2006 doi:10.1152/ajprenal.00190.2006.-Collecting duct (CD)-derived endothelin-1 (ET-1) inhibits renal Na reabsorption and its deficiency increases blood pressure (BP). The role of CD endothelin B (ETB) receptors in mediating these effects is unknown. CD-specific knockout of the ETB receptor was achieved using an aquaporin-2 promoter-Cre recombinase transgene and the loxP-flanked ETB receptor gene (CD ETB KO). Systolic BP in mice with CD-specific knockout of the ETB receptor, ETA receptor (CD ETA KO) and ET-1 (CD ET-1 KO), and their respective controls were compared during normal-and high-salt diet. On a normal-sodium diet, CD ETB KO mice had elevated BP, which increased further during high salt feeding. However, the degree of hypertension in CD ETB KO mice and the further increase in BP during salt feeding were lower than that of CD ET-1 KO mice, whereas CD ETA KO mice were normotensive. CD ETB KO mice had impaired sodium excretion following acute sodium loading. Aldosterone and plasma renin activity were decreased in CD ETB KO mice on normal-and high-sodium diets, while plasma and urinary ET-1 levels did not differ from controls. In conclusion, the CD ETB receptor partially mediates the antihypertensive and natriuretic effects of ET-1. CD ETA and ETB receptors do not fully account for the antihypertensive and natriuretic effects of CD-derived ET-1, suggesting paracrine effects of this peptide. blood pressure; urinary sodium excretion; cell-specific gene targeting NUMEROUS LINES OF EVIDENCE indicate that collecting duct (CD)-derived endothelin-1 (ET-1) is an important regulator of renal Na reabsorption and systemic blood pressure (BP). First, the CD is the major renal site of ET-1 production (8,25,41,48,49), synthesizing more of the peptide than any other cell type (24). Second, the distribution of ET receptors in the kidney closely corresponds to the sites of ET production. Binding and RT-PCR studies using microdissected nephron segments indicate that endothelin receptors are primarily expressed by the inner medullary CD, moderately expressed by outer medullary CD and cortical CD, with much lower expression by other nephron segments (43,45). Third, cultured inner medullary CD cells secrete ET-1 from, and bind ET-1 to, the same (basolateral) side (27). Fourth, in vitro studies indicate that ET-1 inhibits CD Na transport. ET-1 decreases Na reabsorption by the isolated CD, an effect that may be mediated by inhibition of amiloride-sensitive sodium channel activity (14,31,32,46) and/or Na-K-ATPase activity (53). Perhaps the most compelling evidence implicating CD-derived ET-1 in the regulation of renal Na excretion and BP comes from gene targeting studies. Mice with CD-specific knockout of the ET-1 gene (CD ET-1 KO) are hypertensive on a normal-Na diet and this is exacerbated by high Na intake, with systolic BP increasing by almost 40...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

Ge¹,

Bagnall²,

Stricklett³

et al. 2006

American Journal of Physiology-Renal Physiology

190

152

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“…In the inner medulla, labeling of IMCD epithelium was faint. Previously, ET-1 actions have been observed in cortical collecting ducts and distal tubules (Korbmacher et al 1993;Kurokawa et al 1993;Tomita et al 1993). However, studies by Hocher et al (1996) and Terada et al (1992) did not demonstrate ET A receptor mRNA in rat cortical tubules.…”

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

Wendel

Knels

Kummer

et al. 2006

J Histochem Cytochem.

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(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.

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“…ET-1 inhibits vasopressin-stimulated (AVP-stimulated) water flux in isolated CCD (9,12) and reduces AVP-stimulated cyclic AMP accumulation (13)(14)(15) and osmotic water permeability (16,17) in isolated IMCDs. ET-1 also inhibits mineralocorticoid and AVP-stimulated Na and Cl reabsorption in isolated CCDs (12,18,19) and decreases Na/K-ATPase activity in suspensions of IMCDs (20). Despite these data, demonstrating such an ET-1 effect in vivo and clarifying how CD-derived ET-1 physiologically regulates Na and water transport has been problematic.…”

Section: Introductionmentioning

confidence: 99%

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

Ahn¹,

Ge²,

Stricklett³

et al. 2004

J. Clin. Invest.

228

158

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In vitro studies suggest that collecting duct-derived (CD-derived) endothelin-1 (ET-1) can regulate renal Na reabsorption; however, the physiologic role of CD-derived ET-1 is unknown. Consequently, the physiologic effect of selective disruption of the ET-1 gene in the CD of mice was determined. Mice heterozygous for aquaporin2 promoter Cre recombinase and homozygous for loxP-flanked exon 2 of the ET-1 gene (called CD-specific KO of ET-1 [CD ET-1 KO] mice) were generated. These animals had no CD ET-1 mRNA and had reduced urinary ET-1 excretion. CD ET-1 KO mice on a normal Na diet were hypertensive, while body weight, Na excretion, urinary aldosterone excretion, and plasma renin activity were unchanged. CD ET-1 KO mice on a high-Na diet had worsened hypertension, reduced urinary Na excretion, and excessive weight gain, but showed no differences between aldosterone excretion and plasma renin activity. Amiloride or furosemide reduced BP in CD ET-1 KO mice on a normal or high-Na diet and prevented excessive Na retention in salt-loaded CD ET-1 KO mice. These studies indicate that CD-derived ET-1 is an important physiologic regulator of renal Na excretion and systemic BP. IntroductionEndothelin-1 (ET-1) was initially described as a potent endothelial cell-derived vasoconstrictor (1); however, the peptide is now known to be produced by many cell types and to elicit multiple biologic effects (2). The kidney is likely an important target; ET-1 causes renal vasoconstriction, mesangial cell contraction, glomerular cell proliferation, ECM accumulation, and alterations in nephron fluid and electrolyte transport (2). While many renal cell types synthesize and bind ET-1, the collecting duct (CD) is of particular importance: The renal inner medulla contains the highest concentration of ET-1 in the body (3), and the inner medullary CD (IMCD) is the predominant renal site of ET-1 production (4-8) and receptor expression (9-11).In vitro studies suggest that ET-1 inhibits Na and water reabsorption in the cortical CD (CCD) and IMCD and that this occurs through activation of the ET B receptor (ETRB). ET-1 inhibits vasopressin-stimulated (AVP-stimulated) water flux in isolated CCD (9, 12) and reduces AVP-stimulated cyclic AMP accumulation (13-15) and osmotic water permeability (16, 17) in isolated IMCDs. ET-1 also inhibits mineralocorticoid and AVP-stimulated Na and Cl reabsorption in isolated CCDs (12,18,19) and decreases Na/K-ATPase activity in suspensions of IMCDs (20). Despite these data, demonstrating such an ET-1 effect in vivo and clarifying how CD-derived ET-1 physiologically regulates Na and water transport has been problematic. This difficulty stems, in part, from

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Regulation of cortical collecting duct function: Effect of endothelin

Cited by 33 publications

References 21 publications

Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

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

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

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Regulation of cortical collecting duct function: Effect of endothelin

Cited by 33 publications

References 21 publications

Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention

Distribution of Endothelin Receptor Subtypes ETA and ETB in the Rat Kidney

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

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