Effects of Endothelin on Renal Hemodynamics and Renal Function in Anesthetized Dogs

Miura, Katsuyuki; Yukimura, Tokihito; Yamashita, Yutaka; Shichino, Kiyoyuki; Shimmen, Tomoji; Saito, Minoru; Okumura, Michiaki; Imanishi, Masaki; Yamanaka, Shinya; Yamamoto, Kiyoko

doi:10.1093/ajh/3.8.632

Cited by 14 publications

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“…Therefore, in the upper dose range, GHP decreased concomitantly with RBF. Such changes in RBF and GHP can result in severe decreases in GFR, such as those reported by Miura et al 8 In their study, GFR fell by as much as 75% with a dose of 5.0 ng/kg per minute.…”

Section: Discussionsupporting

confidence: 56%

“…5 -7 Some studies have reported that in low doses the effects of ET-1 on RBF were much greater than those on GFR. In the studies by King et al 6 and Miura et al, 8 ET-1 reduced RBF by as much as 20% and did not significantly alter GFR. These findings suggested that ET-1 had a predominant effect on the efferent arterioles, so that the glomerular capillary hydraulic pressure could be elevated or maintained despite the fall in RBF.…”

Section: Effect Of Endothelin-1 On Glomerular Hydraulic Pressure and mentioning

confidence: 88%

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Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

et al. 1993

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The present study was designed to analyze quantitatively the effects of a wide range of endothelin-1 levels on renal hemodynamlcs and renin release in the canine nonftltering kidney, including their effects on glomerular hydraulic pressure. Intrarenal infusion of endothelin-1 produced dose-dependent reductions in renal blood flow, but it did not affect glomerular hydraulic pressure until the infused dose reached high rates. At the rate of 1.0 ng/kg per minute, endothelin-1 reduced renal blood flow by 23% (><0.01), whereas glomerular hydraulic pressure was not significantly changed from 68.1 ±1.3 to 67.4 ± 1.2 mm Hg. However, with a higher rate of endothelin-1 infusion (5.0 and 10.0 ng/kg per minute), glomerular hydraulic pressure fell to 59.5±1.3 and 5L5±1.8 mm Hg (p<0.01), whereas renal blood flow was reduced from 154.5±15 to 83.0±9.5 and 53.5±9.9 mL/min, respectively. Endothelin-1 infusion also produced an inhibitory effect on renin release. With infusion at 1.0 ng/kg per minute, renin release fell from the control level of 47.9±5.6 to 26.6±4.9 units/min per gram kidney weight (p<0.01), and it fell further to 16.1 ±4.3 units/min per gram kidney weight with infusion at 10.0 ng/kg per minute. In summary, endothelin-1 infusion did not affect glomerular hydraulic pressure despite a fall in renal blood flow at low doses, but at high doses it reduced both, suggesting that endothelin-1 exerts separate, dose-dependent effects on preglomerular and postglomerular resistances. In addition, the present study demonstrated that endothelin-1 infusion has an ability to inhibit renin release in vivo when the macula densa-medlated pathway is eliminated. ndothelin-1 (ET-1) has been found in renal glomerular endothelial cells 1 and other kidney cells, 23 and it has specific binding sites in the glomeruli; therefore, the possibility has been raised that ET-1 may play some functional role in the regulation of renal hemodynamics. 4 In vivo, ET-1 has been reported to have potent renal vasoconstrictor effects, acting on both renal blood flow (RBF) and glomerular filtration rate (GFR) in dogs, rats, and rabbits.5 -7 Some studies have reported that in low doses the effects of ET-1 on RBF were much greater than those on GFR. In the studies by King et al 6 and Miura et al,8 ET-1 reduced RBF by as much as 20% and did not significantly alter GFR. These findings suggested that ET-1 had a predominant effect on the efferent arterioles, so that the glomerular capillary hydraulic pressure could be elevated or maintained despite the fall in RBF. King and Brenner 4 also found in rats that the transglomerular capillary pressure gradient was greater in the ET-1 infusion group than that in the control group. However, the direct effect of ET-1 on regulation of glomerular hydraulic pressure (GHP) over the complete dose range has not been fully analyzed. In addition to its potent renal vasoconstriction, ET-1 may have effects on the renin-angiotension system. Although many in vitro studies have found that ET-1 exerts an inhibitory effect on renin releas...

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Section: Discussionsupporting

confidence: 56%

Section: Effect Of Endothelin-1 On Glomerular Hydraulic Pressure and mentioning

confidence: 88%

Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

et al. 1993

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Clinical significance of plasma endothelin-1 in patients with chronic liver disease

et al. 1994

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To determine the clinical significance of plasma endothelin-1 in chronic liver disease, these levels were measured by radioimmunoassay. The plasma endothelin-1 levels in patients with cirrhosis (N = 16) (2.04 +/- 0.25 pg/ml) and patients with hepatocellular carcinoma (N = 22) (2.23 +/- 0.17 pg/ml) increased significantly compared with controls (N = 16) (1.17 +/- 0.17 pg/ml) and patients with chronic hepatitis (N = 11) (1.09 +/- 0.19 pg/ml) (P < 0.01). The presence of ascites rather than tumor volume was associated with a significant elevation of endothelin-1. Endothelin-1 showed significant negative correlations with parameters of hepatic function, including indocyanine green clearance, serum albumin, and prothrombin time. Although endothelin-1 was not correlated with plasma renin activity and plasma endotoxin, it demonstrated a significant positive correlation with the plasma level of atrial natriuretic peptide (r = 0.42, P < 0.01). These findings demonstrate that plasma endothelin-1 increased in proportion to the severity of liver damage and may be causally related with the derangement of systemic/renal hemodynamics and fluid and electrolyte homeostasis seen in advanced liver disease.

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Renal vasodilating and diuretic actions of a selective endothelin ETB receptor agonist, IRL1620

Yukimura

Yamashita

Miura

et al. 1994

European Journal of Pharmacology

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Effects of Endothelin on Renal Hemodynamics and Renal Function in Anesthetized Dogs

Cited by 14 publications

References 0 publications

Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

Effect of endothelin-1 on glomerular hydraulic pressure and renin release in dogs.

Clinical significance of plasma endothelin-1 in patients with chronic liver disease

Renal vasodilating and diuretic actions of a selective endothelin ETB receptor agonist, IRL1620

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