Endothelin induces an increase in renal vascular resistance and a fall in glomerular filtration rate in the rabbit isolated perfused kidney

Cairns, Hugh; Rogerson, Mary; Fairbanks, Lynette D.; Neild, Guy H.; Westwick, John

doi:10.1111/j.1476-5381.1989.tb16876.x

Cited by 42 publications

(13 citation statements)

References 26 publications

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“…Cairns et al reported the possibility that ET-1 at a pressor dose reduced the GFR by vasoconstriction of the afferent glomerular vessels in the rabbit PK [10]. We also observed a large increase in perfusion pressure with a reduction in the GFR following infusion of a high dose of ET-3, suggesting contraction of the renal arteries.…”

Section: Discussionsupporting

confidence: 63%

Effect of Endothelin-3(ET-3) on Renal Function in Rat Perfused Kidney.

et al. 1991

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Abstract. We examined the effect of endothelin-3 (ET-3) at a high dose (pressor dose) and a low dose (non-pressor dose) in rat perfused kidney (PK), since ET-3 has recently been reported to exert a vasodilator action especially at a low dose. Kidneys were perfused with Krebs-Henseleit buffer at a fixed (saline; n=6), 10-13M ET-3 (low dose; n=6) or 10-8M ET-3 (high dose; n=6) was added to the perfusate, and sample collection was performed for the same period with each. The high dose of ET-3 significantly increased the perfusion pressure, fractional sodium excretion and synthesis of prostaglandins (PGs) consistently with a significant reduction in the glomerular filtration rate (GFR). On the other hand, the low dose of ET-3 significantly increased the GFR, urine volume and free-water clearance with no change in the perfusion pressure or synthesis of PGs. These findings suggest that a low dose of ET-3 can increase the glomerular capillary ultrafiltration coefficient and that ET-3 exerts an influence on sodium and water handing in the rat PK.

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Section: Discussionsupporting

confidence: 63%

Effect of Endothelin-3(ET-3) on Renal Function in Rat Perfused Kidney.

et al. 1991

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“…Intrarenal infusion of ET-1 decreases renal blood flow and glomerular filtration rate while increasing sodium excretion. 3,7,8 Previous studies have demonstrated that ET-1 constricts the afferent arteriole 9 -13 ; however, the preglomerular vascular smooth muscle cellular signaling mechanisms responsible are not well understood. ET-1 activates G proteins that in turn stimulate phospholipase C and subsequent release of intracellular calcium ions ([Ca 2ϩ ] i ), leading to vascular smooth muscle cell contraction.…”

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confidence: 99%

Cytochrome P450 and Cyclooxygenase Metabolites Contribute to the Endothelin-1 Afferent Arteriolar Vasoconstrictor and Calcium Responses

et al. 2000

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Abstract-Arachidonic acid metabolites contribute to the endothelin-1 (ET-1)-induced decrease in renal blood flow, but the vascular sites of action are unknown. Experiments performed in vitro used the rat juxtamedullary nephron preparation combined with videomicroscopy. The response of afferent arterioles to ET-1 was determined before and after cytochrome P450 (CYP450) or cyclooxygenase (COX) inhibition. Afferent arteriolar diameter averaged 20Ϯ1 m (nϭ17) at a renal perfusion pressure of 100 mm Hg. Superfusion with 0.001 to 10 nmol/L ET-1 caused a graded decrease in diameter of the afferent arteriole. Vessel diameter decreased by 30Ϯ2% and 41Ϯ2% in response to 1 and 10 nmol/L ET-1, respectively. The afferent arteriolar response to ET-1 was significantly attenuated during administration of the CYP450 hydroxylase inhibitor , such that afferent arteriolar diameter decreased by 19Ϯ3% and 22Ϯ3% in response to 1 and 10 nmol/L ET-1, respectively. COX inhibition also greatly attenuated the vasoconstriction elicited by ET-1, whereas the CYP450 epoxygenase inhibitor N-methylsulfonyl-6-(2-proparglyoxyphenyl) hexanamide enhanced the ET-1-mediated vascular response. Additional studies were performed using freshly isolated smooth muscle cells prepared from preglomerular microvessels. Renal microvascular smooth muscle cells were loaded with the calcium-sensitive dye fura 2 and studied by use of single-cell fluorescence microscopy. Basal renal microvascular smooth muscle cell [Ca 2ϩ ] i averaged 95Ϯ3 nmol/L (nϭ42). ET-1 (10 nmol/L) increased microvascular smooth muscle cell [Ca 2ϩ ] i to a peak value of 731Ϯ75 nmol/L before stabilizing at 136Ϯ8 nmol/L. Administration of DDMS or the COX inhibitor indomethacin significantly attenuated the renal microvascular smooth muscle cell calcium response to ET-1. These data demonstrate that CYP450 hydroxylase and COX arachidonic acid metabolites contribute importantly to the afferent arteriolar diameter and renal microvascular smooth muscle cell calcium responses elicited by ET-1. Key Words: endothelin-1 Ⅲ renal hemodynamics Ⅲ cytochrome P450 Ⅲ cyclooxygenase Ⅲ cytosolic calcium Ⅲ microcirculation E ndothelin-1 (ET-1) is a 21-amino-acid peptide synthesized by endothelial cells that acts as a potent vasoconstrictor on vascular smooth muscle cells. [1][2][3] Elevations in circulating and tissue ET-1 levels have been implicated in a number of pathological states, including acute renal failure, cyclosporine nephrotoxicity, and hypertension. 4 -6 The ET-1 effects on the renal circulation are consistent with the view that the peptide plays a crucial role in maintaining fluid and electrolyte homeostasis. Intrarenal infusion of ET-1 decreases renal blood flow and glomerular filtration rate while increasing sodium excretion. 3,7,8 Previous studies have demonstrated that ET-1 constricts the afferent arteriole 9 -13 ; however, the preglomerular vascular smooth muscle cellular signaling mechanisms responsible are not well understood. ET-1 activates G proteins that in turn stimulate phospholipase C...

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“…The systemic vasodila tor response to ET-1 in rats is blocked by previous administration of nitric oxide synthetase inhibitors (7). ET-1 increases renal vascular resistance in the isolated perfused rabbit kidney (IPK); and at this level, its action is only slightly increased by inhibitors of endothelium-derived relaxing factor, methylene blue and hemoglobin (8).…”

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confidence: 99%

Effect of Endothelin (ET)-1, ET-3 and ET-(16-21) on the Isolated and Perfused Rat Kidney from Normotensive and Spontaneously Hypertensive Rats

Evangelista

Maggi

Castellucci

1992

Japanese Journal of Pharmacology

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ABSTRACT-We have investigated the effect of endothelin (ET)-1, ET-3 and ET-(16-21) on isolated and perfused rat kidney (IPK). ET-1 and ET-3 produced a similar dose-dependent increase in perfusion pressure of IPK, while ET-(16-21) was completely inactive. The ET-1 effects were greater in spon taneously hypertensive rats (SHR) as compared to normotensive rats (WKYR), whereas the ET-3 effects were greater in the SHR group only at the lowest doses. The pressure response of IPK induced by ET-1 was partially modified by prior application of the nitric oxide synthetase inhibitor L-nitroargi nine in both WKYR and SHR.Keywords: Endothelin, Isolated and perfused kidney, Spontaneously hypertensive ratsPeptides of the endothelin (ET) family exert power ful vascular effects (vasodilation and/or vasoconstric tion) that are greatly variable, depending on the type of preparation used (isolated blood vessels, intact animals etc.), species, dose and route of delivery. ET receptors are present in the kidney (1, 2). Several lines of data implicate ETs in renal pathophysiology such as acute renal failure (3, 4). ETs produce powerful vasoconstric tions of isolated renal arteries (5, 6) and an enhanced response to these peptides has been reported in spon taneously hypertensive rats (5). The systemic vasodila tor response to ET-1 in rats is blocked by previous administration of nitric oxide synthetase inhibitors (7). ET-1 increases renal vascular resistance in the isolated perfused rabbit kidney (IPK); and at this level, its action is only slightly increased by inhibitors of endothelium-derived relaxing factor, methylene blue and hemoglobin (8).The aim of this study was to compare the pressor re sponse of the rat IPK to ET-1 and ET-3 in normal and spontaneously hypertensive rats (SHR) and the possible modulatory influence of nitric oxide production by studying the effect of L-nitroarginine on the response to ET-1. In addition, we also investigated the effect of the C-terminal fragment, ET-(16-21), common to both ET 1 and ET-3, which has been reported to possess ET-like agonist activity at some but not all ET receptors (9). Male albino rats, 6-month old normotensive Wistar Kyoto (WKYR) or age-matched spontaneously hypertensive (SHR), Charles-River strain (350 400 g) were anesthetized with ethyl ether, and the kidneys were isolated and perfused as follows: laparatomy was performed via a midline incision; one of the kidneys was exposed; and the renal artery was cannulated with catheter PE G-22, 0.8 mm of diameter. Then the kid ney was removed and placed in a wet organ chamber where it was perfused with a solution of normal Tyrode at a constant rate of 3 ml/min by means of a peristaltic pump. The perfusion pressure was measured with a Bentley-Trantec pressure transducer and recorded on a polygraph. After a 30-min stabilization-period, the nor mal Tyrode solution was replaced with a solution con taining increasing concentrations of ET-1 (0.03 3 nM), ET-3 (0.03 3 nM) or ET-(16-21) (up to 1 u M) or with a maximal vasoconstrictor dose of norad...

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Endothelin induces an increase in renal vascular resistance and a fall in glomerular filtration rate in the rabbit isolated perfused kidney

Cited by 42 publications

References 26 publications

Effect of Endothelin-3(ET-3) on Renal Function in Rat Perfused Kidney.

Effect of Endothelin-3(ET-3) on Renal Function in Rat Perfused Kidney.

Cytochrome P450 and Cyclooxygenase Metabolites Contribute to the Endothelin-1 Afferent Arteriolar Vasoconstrictor and Calcium Responses

Effect of Endothelin (ET)-1, ET-3 and ET-(16-21) on the Isolated and Perfused Rat Kidney from Normotensive and Spontaneously Hypertensive Rats

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