Immunoreactive endothelin in rat kidney inner medulla: Marked decrease in spontaneously hypertensive rats

Kïtamura, Kazuo; Tanaka, Tomoko; Kato, Jun; Ogawa, Tsuneo; Eto, Tanenao; Tanaka, Kenjiro

doi:10.1016/0006-291x(89)91958-x

Cited by 116 publications

(64 citation statements)

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“…This cell line was selected because the inner medulla is an important site for ET-1 action in vivo and because this cell line has been validated as a model for aldosterone action (52)(53)(54)(55)(56). Edn1 mRNA exhibited a dose-dependent increase in the presence of aldosterone that was significant at concentrations as low as 0.1 M (Fig.…”

Section: Aldosterone Stimulates Et-1 Inmentioning

confidence: 99%

Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Stow

Gumz

Lynch

et al. 2009

Journal of Biological Chemistry

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Aldosterone and endothelin-1 (ET-1) act on collecting duct cells of the kidney and are important regulators of renal sodium transport and cardiovascular physiology. We recently identified the ET-1 gene (edn1) as a novel aldosterone-induced transcript. However, aldosterone action on edn1 has not been characterized at the present time. In this report, we show that aldosterone stimulated edn1 mRNA in acutely isolated rat inner medullary collecting duct cells ex vivo and ET-1 peptide in rat inner medulla in vivo. Aldosterone induction of edn1 mRNA occurred in cortical, outer medullary, and inner medullary collecting duct cells in vitro. Inspection of the edn1 promoter revealed two putative hormone response elements. Levels of heterogeneous nuclear RNA synthesis demonstrated that edn1 mRNA stimulation occurred at the level of transcription. RNA knockdowns corroborated pharmacological studies and demonstrated both mineralocorticoid receptor and glucocorticoid receptor participated in this response. Aldosterone resulted in dose-dependent nuclear translocation and binding of mineralocorticoid receptor and glucocorticoid receptor to the edn1 hormone response elements. Hormone receptors mediated the association of chromatin remodeling complexes, histone modification, and RNA polymerase II at the edn1 promoter. Direct interaction between aldosterone and ET-1 has important implications for renal and cardiovascular function.The steroid hormone aldosterone is critical for sodium homeostasis and blood pressure control. Aldosterone works by modulating the fine regulation of sodium reabsorption in the distal nephron and collecting duct of the kidney. Classic aldosterone action is mediated through the mineralocorticoid receptor (MR), 3 a member of the nuclear receptor family of proteins that function as ligand-dependent transcription factors (1). MR acts on cells of the distal nephron and collecting duct to stimulate transcription of genes involved in transepithelial sodium transport, including the epithelial sodium channel ␣ subunit (scnn1a, ␣ENaC), the sodium, potassium-ATPase ␣1 subunit (atp1a1), and the serum-and glucocorticoid-regulated kinase-1 (sgk1) (2). The increase in expression of genes involved in sodium transport results in net sodium reabsorption followed by in increase in extracellular fluid volume and a consequent increase in blood pressure. Indeed, MR antagonists such as spironolactone and eplerenone are used clinically as diuretic and anti-hypertensive agents (3). The mechanism of MR action is consistent with a classic steroid receptor mechanism (4). Prior to activation MR resides in the cytosol. Ligand binding induces a conformational change that releases chaperone proteins and reveals a nuclear localization signal. Nuclear MR binds directly to DNA at hormone response elements (HREs) in target genes to modulate their transcription. A typical HRE for MR consists of two receptor binding half-sites with the consensus sequence 5Ј-TGTTCT-3Ј, arranged as an inverted palindrome (1, 5). These HREs facilitate binding of...

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Section: Aldosterone Stimulates Et-1 Inmentioning

confidence: 99%

Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Stow

Gumz

Lynch

et al. 2009

Journal of Biological Chemistry

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“…The highest concentrations of immunoreactive ET-1 in the body have been detected in the renal medulla (23). In addition, gene expression and immunoreactive peptides of ET-1 and its receptors have been demonstrated in the renal tissue, especially in the medullary region (23,26,40,42,45). Interestingly, in vivo studies revealed that administration of ET-1 resulted in reduced renal hemodynamics and kidney dysfunction, similar to those found during pneumoperitoneum (9).…”

mentioning

confidence: 90%

mentioning

confidence: 99%

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

Abassi

Bishara²,

Karram³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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The mechanism underlying this phenomenon is largely unknown. This study was designed to investigate the involvement of endothelin (ET)-1 and nitric oxide (NO) systems in IAP-induced renal dysfunction. Rats were subjected to IAP of 14 mmHg for 1 h, followed by a deflation for 60 min (recovery). Four additional groups were pretreated with 1) ABT-627, an ET A antagonist; 2) A-192621, an ETB antagonist; 3) nitroglycerine; and 4) N G -nitro-L-arginine methyl ester, a NO synthase inhibitor, before IAP. Urine flow rate (V), absolute Na ϩ excretion (UNaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. Significant reductions in kidney function and hemodynamics were observed when IAP was applied. V decreased from 8.1 Ϯ 1.0 to 5.8 Ϯ 0.5 l/min, UNaV from 1.08 Ϯ 0.31 to 0.43 Ϯ 0.10 eq/min, GFR from 1.84 Ϯ 0.12 to 1.05 Ϯ 0.06 ml/min (Ϫ46.9 Ϯ 2.7% from baseline), and RPF from 8.62 Ϯ 0.87 to 3.82 Ϯ 0.16 ml/min (Ϫ54 Ϯ 3.5% from baseline). When the animals were pretreated with either ABT-627 or A-192621, given alone or combined, the adverse effects of IAP on GFR, RPF, V, and UNaV were significantly augmented. When the animals were pretreated with nitroglycerine, the adverse effects of pneumoperitoneum on GFR and RPF were substantially improved. In contrast, pretreatment with N G -nitro-L-arginine methyl ester remarkably aggravated pneumoperitoneum-induced renal dysfunction. In conclusion, decreased renal excretory function and hypofiltration are induced by increased IAP. These effects are related to impairment of renal hemodynamics and could be partially ameliorated by pretreatment with nitroglycerine and aggravated by NO and ET blockade.rat; intra-abdominal pressure PNEUMOPERITONEUM AT PRESSURE above 10 mmHg during laparoscopic surgery has been shown to produce transient oliguria and reduced glomerular filtration rate (GFR) and renal blood flow (RBF) (3,9,16,33,34). Despite much research in this field, the systemic physiological consequences of CO 2 pneumoperitoneum and the mechanisms underlying its adverse effects on renal hemodynamics and excretory function are not fully understood (9). However, there is compelling experimental evidence that the adverse renal effects induced by pneumoperitoneum are affected by the level of intra-abdominal pressure (IAP), volume status, degree of hypercarbia, positioning, and individual hemodynamic and renal reserves (9, 10). Additional factors that may affect renal function during pneumoperitoneum include direct compression of the renal parenchyma and renal vein (4, 17), increased resistance in the renal vasculature (47), and release of vasoconstrictors, such as vasopressin, angiotensin II, catecholamines, and endothelin (ET)-1 (1, 13). The latter is a very potent natural mammalian vasoconstrictor agent (25), acting on the cardiovascular and renal systems and other target organs by binding to two major types of receptors, ET A and ET B (2,25,36). High abundance of ET A receptors has been detected in the aorta, heart, and kidney, whereas ET B receptors are expre...

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“…In the SHR, however, both circulating and vascular endothelin is suppressed. Similarly, in the renal medulla of the SHR, the endothelin content is reduced [78]. These experimental findings suggest that endothelin may be differently involved in different forms of hypertension, possibly also in the human.…”

mentioning

confidence: 65%

Endothelin in renal disease: role of endothelin antagonists

Wenzel

1995

Nephrology Dialysis Transplantation

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Immunoreactive endothelin in rat kidney inner medulla: Marked decrease in spontaneously hypertensive rats

Cited by 116 publications

References 3 publications

Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Aldosterone Modulates Steroid Receptor Binding to the Endothelin-1 Gene (edn1)

Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

Endothelin in renal disease: role of endothelin antagonists

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