Plasma endothelin-1 and -3 in cirrhosis: relationship with systemic hemodynamics, renal function and neurohumoral systems

Cross-linked hemoglobin (XL-Hb) infused into dogs increases mean arterial pressure (MAP) but decreases blood flow to the renal (RBF), mesenteric (MBF), and iliac (IBF) circulations. These actions differ markedly from dextran infusion (which increases RBF, MBF, and IBF without altering MAP) and may be due to scavenging of nitric oxide by XL-Hb. However, because the hormonal milieu regulating regional circulation is altered during hemorrhage (when XL-Hb may be used), we studied whether systemic hemodynamics, RBF, MBF, IBF, and renal excretory function in hemorrhaged dogs was altered when resuscitated with XL-Hb compared with dextran ( n = 6 each). Hemorrhage decreased MAP by 25% due to a 75% decline in cardiac output. RBF, MBF, and IBF all fell by 33, 64, and 72%, respectively ( P < 0.05 each). There was also a fall in glomerular filtration rate (GFR), urinary flow, and sodium excretion ( P < 0.05 each). After resuscitation, MAP, cardiac output, RBF, MBF, IBF, and GFR all recovered to basal values with either XL-Hb or dextran. Urinary flow and sodium excretion increased to above basal levels with dextran (both by 3.5-fold; P < 0.05) or XL-Hb (by 7.5- and 10-fold, respectively; P < 0.05). We conclude that resuscitation with XL-Hb after hemorrhage not only increases MAP, but also restores RBF, MBF, IBF, GFR, and urinary sodium and volume excretion analogously to dextran. The results contrast with those in normal dogs and suggest that nitric oxide inhibition does not impair hemodynamic and renal function recovery during hemorrhage.

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Oestrogen protects against ischaemic acute renal failure in rats by suppressing renal endothelin-1 overproduction

Clinical Science ◽

10.1042/cs103s434s ◽

2002 ◽

Vol 103 (s2002) ◽

pp. 434S-437S ◽

Cited By ~ 27

Author(s):

Masanori TAKAOKA ◽

Mikihiro YUBA ◽

Toshihide FUJII ◽

Mamoru OHKITA ◽

Yasuo MATSUMURA

Keyword(s):

Renal Failure ◽

Renal Function ◽

Acute Renal Failure ◽

Renal Dysfunction ◽

Tissue Injury ◽

Male Rats ◽

Left Renal Artery ◽

Protective Effects ◽

Endothelin 1 ◽

Ischaemia Reperfusion

We investigated whether the treatment with 17β-oestradiol has renal protective effects in male rats with ischaemic acute renal failure (ARF). We also examined if the effect of 17β-oestradiol is accompanied by suppression of enhanced endothelin-1 production in postischaemic kidneys. Ischaemic ARF was induced by clamping the left renal artery and vein for 45min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function parameters such as blood urea nitrogen, plasma creatinine and creatinine clearance were measured to test the effectiveness of the steroid hormone. Renal function in ARF rats markedly decreased 24h after reperfusion. The ischaemia/reperfusion-induced renal dysfunction was dose-dependently improved by pretreatment with 17β-oestradiol (20 or 100µg/kg, intravenously). Histopathological examination of the kidney of untreated ARF rats revealed severe lesions, such as tubular necrosis, proteinaceous casts in tubuli and medullary congestion, all of which were markedly improved by the higher dose of 17β-oestradiol. In addition, endothelin-1 content in the kidney after the ischaemia/reperfusion increased significantly by approx. 2-fold over sham-operated rats, and this elevation was dose-dependently suppressed by the 17β-oestradiol treatment. These results suggest that oestrogen exhibits protective effects against renal dysfunction and tissue injury induced by ischaemia/reperfusion, possibly through the suppression of endothelin-1 overproduction in postischaemic kidneys.

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Effects of endothelin-1 on renal function and renin secretion in vivo and in vitro

European Journal of Pharmacology ◽

10.1016/0014-2999(90)92135-6 ◽

1990 ◽

Vol 183 (5) ◽

pp. 1814-1815

Author(s):

S. Morimoto ◽

K. Hisaki ◽

K. Nakase ◽

R. Ikegawa ◽

K. Hayashi ◽

...

Keyword(s):

Renal Function ◽

Renin Secretion ◽

Endothelin 1

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Fibroblast growth factor 23 and renal function among young and healthy individuals

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-1183 ◽

2018 ◽

Vol 56 (9) ◽

pp. 1483-1489 ◽

Cited By ~ 1

Author(s):

Raffaele Bernasconi ◽

Stefanie Aeschbacher ◽

Steffen Blum ◽

Michel Mongiat ◽

Marc Girod ◽

...

Keyword(s):

Renal Function ◽

Fibroblast Growth Factor 23 ◽

Phosphate Metabolism ◽

Fibroblast Growth ◽

Healthy Individuals ◽

Endothelin 1 ◽

Phosphate Excretion ◽

Unit Increase ◽

Fgf 23 ◽

Relationship Of

Abstract Background: Fibroblast growth factor 23 (FGF-23), an osteocyte hormone involved in the regulation of phosphate metabolism, is associated with incident and progressive chronic kidney disease. We aimed to assess the association of FGF-23 with renal parameters, vascular function and phosphate metabolism in a large cohort of young and healthy individuals. Methods: Healthy individuals aged 25–41 years were included in a prospective population-based study. Fasting venous blood and morning urinary samples were used to measure plasma creatinine, cystatin C, endothelin-1, phosphate and plasma FGF-23 as well as urinary creatinine and phosphate. Multivariable regression models were constructed to assess the relationship of FGF-23 with parameters of renal function, endothelin-1 and fractional phosphate excretion. Results: The median age of 2077 participants was 37 years, 46% were males. The mean estimated glomerular filtration rate (eGFR – CKD-EPI creatinine-cystatin C equation) and fractional phosphate excretion were 110 mL/min/1.73 m2 and 8.7%, respectively. After multivariable adjustment, there was a significant inverse relationship of FGF-23 with eGFR (β per 1 log-unit increase −3.81; 95% CI [−5.42; −2.20]; p<0.0001). Furthermore, we found a linear association between FGF-23 and endothelin-1 (β per 1 log-unit increase 0.06; [0.01, 0.11]; p=0.01). In addition, we established a significant relationship of FGF-23 with fractional phosphate excretion (β per 1 log-unit increase 0.62; [0.08, 1.16]; p=0.03). Conclusions: Increasing plasma FGF-23 levels are strongly associated with decreasing eGFR and increasing urinary phosphate excretion, suggesting an important role of FGF-23 in the regulation of kidney function in young and healthy adults.

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Renomedullary Interstitial Cell Endothelin A Receptors Regulate BP and Renal Function

Journal of the American Society of Nephrology ◽

10.1681/asn.2020020232 ◽

2020 ◽

Vol 31 (7) ◽

pp. 1555-1568

Author(s):

Chunyan Hu ◽

Jayalakshmi Lakshmipathi ◽

Deborah Stuart ◽

Janos Peti-Peterdi ◽

Georgina Gyarmati ◽

...

Keyword(s):

Renal Function ◽

Knockout Mice ◽

Interstitial Cell ◽

Collecting Duct ◽

Interstitial Cells ◽

Water Excretion ◽

Endothelin 1 ◽

Enhanced Production ◽

Endothelin A Receptor ◽

Endothelin A

BackgroundThe physiologic role of renomedullary interstitial cells, which are uniquely and abundantly found in the renal inner medulla, is largely unknown. Endothelin A receptors regulate multiple aspects of renomedullary interstitial cell function in vitro.MethodsTo assess the effect of targeting renomedullary interstitial cell endothelin A receptors in vivo, we generated a mouse knockout model with inducible disruption of renomedullary interstitial cell endothelin A receptors at 3 months of age.ResultsBP and renal function were similar between endothelin A receptor knockout and control mice during normal and reduced sodium or water intake. In contrast, on a high-salt diet, compared with control mice, the knockout mice had reduced BP; increased urinary sodium, potassium, water, and endothelin-1 excretion; increased urinary nitrite/nitrate excretion associated with increased noncollecting duct nitric oxide synthase-1 expression; increased PGE2 excretion associated with increased collecting duct cyclooxygenase-1 expression; and reduced inner medullary epithelial sodium channel expression. Water-loaded endothelin A receptor knockout mice, compared with control mice, had markedly enhanced urine volume and reduced urine osmolality associated with increased urinary endothelin-1 and PGE2 excretion, increased cyclooxygenase-2 protein expression, and decreased inner medullary aquaporin-2 protein content. No evidence of endothelin-1–induced renomedullary interstitial cell contraction was observed.ConclusionsDisruption of renomedullary interstitial cell endothelin A receptors reduces BP and increases salt and water excretion associated with enhanced production of intrinsic renal natriuretic and diuretic factors. These studies indicate that renomedullary interstitial cells can modulate BP and renal function under physiologic conditions.

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Effects of a new dihydropyridine derivative, S12968 (pranedipine), and its stereoisomer, S12967, on renal effects of endothelin-1

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-185 ◽

1994 ◽

Vol 72 (11) ◽

pp. 1294-1298 ◽

Cited By ~ 2

Author(s):

Immaculada Montañés ◽

Olga Flores ◽

Nélida Eleno ◽

José M. López-Novoa

Keyword(s):

Renal Function ◽

Arterial Pressure ◽

Vascular Resistance ◽

Fold Increase ◽

Urine Flow ◽

Renal Vascular Resistance ◽

Potassium Excretion ◽

Endothelin 1 ◽

Dihydropyridine Derivative ◽

Renal Vascular

The purpose of the present study was to assess in rats the prevention by two enantiomers of a new dihydropyridine derivative (pranedipine) (called S12967 for the dextrogyre(+) and S12968 for the levogyre (−) molecules) of the renal and cardiovascular effects induced by endothelin-1. The injection of endothelin-1 (1 nmol/kg body weight) induced a sharp and transient decrease in urine flow, sodium and potassium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow, a significant increase in renal vascular resistance, and a small but significant increase in arterial pressure. Treatment with S12968 alone (0.3 mg/kg) induced a 2.5-fold increase in urine flow and potassium excretion and a 4.5-fold increase in sodium excretion. Pretreatment with S12968 completely blocked the endothelin-1 induced increase in arterial pressure, did not affect the acute effect of endothelin-1 on urine flow, sodium and potassium excretion, filtration rate, and renal blood flow, but blunted the effect on renal vascular resistance. Administration of S12967 alone (1 mg/kg) did not induce changes in either renal function or arterial pressure. In S12967-treated animals, endothelin-1 also induced a transient increase in arterial pressure and renal vascular resistance but failed to change renal function in a significant manner. In summary, the above reported experiments show that at the higher, nonhypotensive doses, the levogyre enantiomer (S12968) of a new dihydropyridine derivative (pranedipine) completely prevented the hypertensive effect of endothelin 1, and partially prevented the effect of endothelin-1 on renal vascular resistance. The dextrogyre enantiomer (S12967) had almost no effect on either mean arterial pressure or renal vascular resistance but completely blocked the endothelin-1-induced decrease in urine flow and urinary sodium excretion.Key words: calcium antagonists, endothelin, dihydropyridines, kidney, renal function (rat).

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