Hemodynamic and tubular effects of endothelin and thromboxane in the isolated perfused rat kidney

Ferrario, Romana G.; Foulkes, Roly; Salvati, Patricia; Patrono, Carlo

doi:10.1016/0014-2999(89)90436-6

Cited by 31 publications

(12 citation statements)

References 19 publications

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“…Similar results were already reported by Ferrarioet al [5] forET-1. These authors used the isolated rat kidney, perfused at constant pressure, in a recirculating system and found a concentration-related reduction in RPF with ET-1 concentrations higher than 10 pmol/l.…”

Section: Discussionsupporting

confidence: 82%

“…Ferrario et al [5] reported a similar and significant increase of G F R (p <0.05) at ET-1 concentrations of 100 pmol/l but did not discuss this finding. In the same study, however, they observed a significant G F R reduction (p <0.01) at 500 pmol/l ET-1 [5]With respect to the ET-3 concentrations used in the present experiments it must be mentioned that endothelins are now consid ered as local factors rather than as circulating hormones. Although ET-3 might be a neural form of endothelins [1].…”

Section: Discussionmentioning

confidence: 54%

“…10]. In addition, endotheiin was found to increase urinary sodium excretion [5] and to inhibit N a+-K 4-ATPase activity in in ner medullary collecting duct cells [11].…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

Schramek

Willinger²,

Gstraunthaler³

et al. 1992

Kidney Blood Press Res

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The present study has been performed to evaluate hemodynamic and tubular effects of various endothelin-3 (ET-3) concentrations on the isolated perfused rat kidney. Using this experimental system we observed a profound reduction of renal perfusate flow at all ET-3 concentrations tested (50, 250 and 500 pmol/l), suggesting that the vasoconstrictive potency of ET-3 in the kidney is comparable to that described for endothelin-1 (ET-1). The effects on glomerular filtration rate (GFR) differed depending on the ET-3 dose applied. While 250 pmol/l ET-3 increased GFR by 30%, 500 pmol/l ET-3 markedly reduced GFR. 50 pmol/l ET-3 did not alter GFR although renal vascular resistance significantly increased. Infusion of 1 µmol/l N-nitro-L-arginine, a specific and potent inhibitor of nitric oxide synthesis in endothelial cells, abolished the GFR elevation induced by 250 pmol/l ET-3. In parallel with the changes of GFR we observed an increase in sodium reabsorption at 250 pmol/l and a decrease of this parameter at 500 pmol/l ET-3. Moreover, an ET-3 concentration (500 pmol/l), which induced a dramatic fall in tubular sodium load, led to an increase of fractional sodium excretion and to a decrease of renal oxygen consumption. We conclude that ET-3 is a potent vasoconstrictor in the isolated perfused rat kidney. Furthermore, it modulates GFR in a differentiated mode, depending on the concentration used. The GFR increase at 250 pmol/l ET-3 seems to be mediated by endothelium-derived nitric oxide. In addition to its glomerular action, ET-3 might also affect tubular sodium transport.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 54%

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Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

Schramek

Willinger²,

Gstraunthaler³

et al. 1992

Kidney Blood Press Res

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“…This finding supports a potential causative role for decreases in ENaC activity driving natriuresis in response to ET-1. This is consistent with findings in the isolated perfused rat kidney and microperfused rabbit CCT, respectively, where nanomolar concentrations of ET-1 increase renal Na ϩ excretion and hyperpolarize the luminal plasma membrane in an amiloride-sensitive manner while increasing the resistance of this membrane (15,27). In agreement are also studies utilizing in vivo administration of endothelin receptor-specific agonists and antagonists.…”

Section: Discussionsupporting

confidence: 79%

Regulation of the epithelial Na⁺channel by endothelin-1 in rat collecting duct

Bugaj

Pochynyuk

Mironova

et al. 2008

American Journal of Physiology-Renal Physiology

100

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We used patch-clamp electrophysiology to investigate regulation of the epithelial Na ϩ channel (ENaC) by endothelin-1 (ET-1) in isolated, split-open rat collecting ducts. ET-1 significantly decreases ENaC open probability by about threefold within 5 min. ET-1 decreases ENaC activity through basolateral membrane ETB but not ETA receptors. In rat collecting duct, we find no role for phospholipase C or protein kinase C in the rapid response of ENaC to ET-1. ET-1, although, does activate src family tyrosine kinases and their downstream MAPK1/2 effector cascade in renal principal cells. Both src kinases and MAPK1/2 signaling are necessary for ET-1-dependent decreases in ENaC open probability in the split-open collecting duct. We conclude that ET-1 in a physiologically relevant manner rapidly suppresses ENaC activity in native, mammalian principal cells. These findings may provide a potential mechanism for the natriuresis observed in vivo in response to ET-1, as well as a potential cause for the salt-sensitive hypertension found in animals with impaired endothelin signaling.salt-sensitive hypertension; systemic blood pressure ENDOTHELIN-1 (ET-1) is a powerful vasoconstricting peptide hormone that is an important regulator of systemic blood pressure (53). Independent of its vascular effects, ET-1 also affects renal Na ϩ and water handling favoring natriuresis and diuresis. While circulating ET-1 arises from endothelial cells, local ET-1 systems also exist. For instance in the kidney, the collecting duct produces significant amounts of 25,38,51). ET-1 targets cells through two distinct receptor subtypes, ET A and ET B (32, 41). Renal collecting duct cells have both types of receptors and are able to bind 49,50). Thus, collecting duct-derived ET-1, acting in a paracrine/ autocrine manner, is an important regulator of renal Na ϩ handling (2,20,26,42).Regulated Na ϩ reabsorption in the renal collecting duct, in part, controls blood pressure. Here, activity of the aldosteronesensitive epithelial Na ϩ channel (ENaC) is limiting for Na ϩ transport (reviewed in Refs. 19,30,31). Dysfunction and inappropriate regulation of ENaC consequently result in improper renal Na ϩ handling and thus, blood pressure disorders. For instance, gain of ENaC function in rodents and humans is causative for hypertension associated with the hallmarks of low plasma renin activity and aldosterone levels (1,22,23,45,46). Amiloride, an ENaC blocker, ameliorates this hypertension.Spotting lethal (sl) rats have a naturally occurring null mutation of ET B (17). These rats, when rescued from lethal intestinal aganglionosis by directed ET B transgene expression in the enteric nervous system, are particularly sensitive to DOCA and salt-induced hypertension (18,33,34). Similarly, mice with collecting duct-specific knockout of the ET B receptor have elevated blood pressure that further increases with high salt feeding (20). Collecting duct-specific ET-1 knockout, moreover, leads to hypertension exacerbated by high salt (2, 42). Plasma renin activity and aldoste...

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“…However, infusion of ET-1 at subpressor doses (10 Ϫ11 -10 Ϫ9 M) in isolated perfused rat kidney caused an increase in urinary sodium excretion with a decrease in GFR and RBF (8). Furthermore, the study by Hsieh et al (13) has demonstrated that the enhanced synthesis of ET-1 in the renal medulla correlates with urinary sodium excretion in the early stage of DOCAsalt-treated rats, suggesting that renal medullary ET-1 is involved in water-electrolyte balance.…”

Section: Discussionmentioning

confidence: 97%

ET_A receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation

Wang¹,

Chen²,

Wang³

2005

American Journal of Physiology-Heart and Circulatory Physiology

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To test the hypothesis that activation of the endothelin type A (ET(A)) receptor contributes to decreased renal excretory function and increased blood pressure in sensory nerve-degenerated rats fed a high-salt diet, neonatal Wistar rats were given vehicle or capsaicin (CAP, 50 mg/kg s.c.) on the first and second day of life. After being weaned, vehicle or CAP-treated rats were fed a normal (NS, 0.5%) or a high- (HS, 4%) sodium diet for 2 wk with or without ABT-627 (5 mg x kg(-1) x day(-1), a selective ET(A) receptor antagonist). Systolic blood pressure increased in CAP-treated rats fed a HS diet (CAP-HS) compared with vehicle-treated rats fed a HS diet (CON-HS, 145 +/- 7 vs. 89 +/- 5 mmHg, P < 0.05). Creatinine clearance and fractional sodium excretion (FE(Na)) decreased in CAP-HS rats compared with CON-HS rats (creatinine clearance, 0.54 +/- 0.05 vs. 0.81 +/- 0.09 ml x min(-1) x 100 g body wt(-1); FE(Na), 8.68 +/- 0.99 vs. 12.53 +/- 1.47%, respectively; P < 0.05). Water and sodium balance increased in CAP-HS rats compared with CON-HS (water balance, 20.2 +/- 1.5 vs. 15.5 +/- 1.9 ml/day; sodium balance, 11.9 +/- 3.1 vs. 2.4 +/- 0.3 meq/day, respectively; P < 0.05). The endothelin (ET)-1 levels in plasma and isolated glomeruli increased by about twofold in CAP-HS rats compared with CON-HS rats (P < 0.05). ABT-627 prevented the decrease in creatinine clearance and FE(Na), the increase in water and sodium balance, and the increase in blood pressure in CAP-HS rats (P < 0.05). Therefore, the blockade of the ET(A) receptor ameliorates the impairment of renal excretory function and prevents the elevation in blood pressure in salt-sensitive hypertension induced by degeneration of sensory nerves, indicating that the activation of the ET(A) receptor impairs renal function and contributes to the development of a salt-induced increase in blood pressure in this model.

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Hemodynamic and tubular effects of endothelin and thromboxane in the isolated perfused rat kidney

Cited by 31 publications

References 19 publications

Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

Regulation of the epithelial Na⁺channel by endothelin-1 in rat collecting duct

ET_A receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation

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Hemodynamic and tubular effects of endothelin and thromboxane in the isolated perfused rat kidney

Cited by 31 publications

References 19 publications

Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

Endothelin-3 Modulates Glomerular Filtration Rate in the Isolated Perfused Rat Kidney

Regulation of the epithelial Na+channel by endothelin-1 in rat collecting duct

ETA receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation

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Resources

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Regulation of the epithelial Na⁺channel by endothelin-1 in rat collecting duct

ET_A receptor blockade prevents renal dysfunction in salt-sensitive hypertension induced by sensory denervation