Cardiovascular and renal actions of endothelin: effects of calcium-channel blockers

Cao, Lequn; Banks, Robert O.

doi:10.1152/ajprenal.1990.258.2.f254

Cited by 16 publications

(13 citation statements)

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“…17,19,20,23,24 The current study represents our initial investigation into the calcium signaling mechanisms in preglomerular vascular smooth muscle cells and reveals signaling pathways similar to those previously described in largecaliber arteries, cultured vascular smooth muscle cells, and endothelial cells. 1,15,17,20,25 In nonrenal vascular smooth muscle, endothelin evokes a biphasic elevation of [Ca 2ϩ ] i by binding to ET A receptors at the cell surface and activating a pertussis toxin-insensitive G-protein that in turn stimulates phospholipase C (PLC).…”

Section: Discussionsupporting

confidence: 60%

“…However, in the renal circulation, evidence suggests the presence of both ET A and ET B receptors that produce vasoconstriction. 7,8,15,20,22,23 To date, there are only limited data demonstrating the functional distribution of ET A and ET B receptors along preglomerular resistance vessels. Endlich et al, 6 using the split hydronephrotic kidney technique, reported that ET B receptor-mediated vasoconstriction was present at both preglomerular and postglomerular sites, whereas ET A receptors are strictly preglomerular.…”

Section: Discussionmentioning

confidence: 99%

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Endothelin-Mediated Calcium Signaling in Preglomerular Smooth Muscle Cells

et al. 2000

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Abstract-This study was performed to test the hypothesis that endothelin peptides differentially influence intracellular calcium concentration ([Ca 2ϩ ] i ) in preglomerular microvascular smooth muscle cells (MVSMC), in part through activation of endothelin (ET) A receptors. Experiments were performed in vitro with the use of single MVSMC freshly isolated from rat preglomerular microvessels. The effect of ET-1, ET-2, and ET-3 on [Ca 2ϩ ] i was measured with the use of the calcium-sensitive dye, fura 2, and standard fluorescence microscopy techniques. Baseline [Ca 2ϩ ] i averaged 84Ϯ3 nmol/L (nϭ141 cells from 23 dispersions). ET-1 concentrations of 1, 10, and 100 nmol/L evoked peak increases in [Ca 2ϩ ] i of 48Ϯ16, 930Ϯ125, and 810Ϯ130 nmol/L, respectively. The time course of the [Ca 2ϩ ] i response was biphasic, beginning with a rapid initial increase followed by a sustained plateau phase or a period during which [Ca 2ϩ ] i oscillated sharply. Similar responses were observed after ET-2 administration. In contrast, ET-3 stimulated monophasic increases in [Ca 2ϩ ] i of only 14Ϯ5, 33Ϯ16, and 44Ϯ19 nmol/L at peptide concentrations of 1, 10, and 100 nmol/L, respectively. These responses are significantly smaller than responses to ET-1 or ET-2, respectively. The relative contributions of calcium mobilization and calcium influx in the response to ET-1 were also evaluated. Removal of calcium from the bathing medium did not significantly alter the peak response to 10 nmol/L ET- influx is postulated to increase smooth muscle contractility and may contribute to the prolonged vasoconstriction commonly associated with endothelin-mediated responses. Initially, the renal vasoconstrictor actions of ET-1 were thought to involve ET A receptors exclusively, with ET B receptors producing vasodilation by stimulating nitric oxide release from endothelial cells. However, the development of selective ET A receptor antagonists revealed that non-ET A receptors contribute some of the ET-1-mediated vasoconstriction. ET B receptor-mediated vasoconstriction has been demonstrated in vivo in the renal circulation of the rat. 5,6 Endothelin receptors have been identified in the kidney, and reports suggest that rat preglomerular microvessels express both ET A and ET B receptors 7,8 ; however, there are only limited data demonstrating the functional distribution of ET A and ET B receptors along preglomerular resistance vessels. 6 Our laboratory has recently established the methods needed for obtaining viable vascular smooth muscle cells from freshly isolated preglomerular microvascular tissue. 9 We used this preparation to determine the effect of receptor selective endothelin peptides on [Ca 2ϩ ] i in preglomerular vascular smooth muscle cells. Additional studies were performed to determine the relative contribution of calcium influx and calcium mobilization on the increase in [Ca 2ϩ ] i induced by endothelin.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Endothelin-Mediated Calcium Signaling in Preglomerular Smooth Muscle Cells

et al. 2000

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“…5-11 ET-1 is a peptide produced by endothelial cells that acts as a vasoconstrictor in most vascular beds, including the renal vasculature. 15,16 Its concentration in the plasma presumably reflects a spillover from local release minus that which is removed from the circulation, and thus is an indirect cumulative measure of release from individual vascular beds. The elevated plasma ET-1 may result from a decreased renal clearance with impaired excretion or metabolism for ET-1, as is the case for many other peptide hormones in chronic renal failure.…”

Section: Discussionmentioning

confidence: 99%

Plasma Endothelin-1 in Hemodialysis Treatment - the Influence of Hypertension

Stefanidis¹,

Wurth²,

Mertens³

et al. 2004

Journal of Cardiovascular Pharmacology

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In patients on chronic hemodialysis hypotensive episodes are frequently encountered during the course of treatment and the prevalence of atherosclerosis is increased. Endothelin-1 (ET-1), an endothelium-derived peptide with vasoconstrictive and mitogenic effects on smooth muscles, is involved in vascular tone regulation and in the pathogenesis of atherosclerosis. The aim of the present study was to investigate plasma ET-1 during hemodialysis treatment and to explore the probable influence of pre-existing hypertension. Forty-seven hemodialysis patients (21 females, mean age 62 +/- 12 years) were evaluated and hypertensive patients (n = 33) were compared to normotensive patients (n = 14). Relative blood volume changes (hemoglobinometry) and blood pressure were measured. Samples were taken before, every hour during and after hemodialysis. Plasma ET-1 was measured by enzyme-linked immunosorbent assay and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration rate of 2224 +/- 933 mL was performed. Total blood volume at the end of hemodialysis was 89.4 +/- 8.2% of the pretreatment volume. The fall in blood pressure (137/74 +/- 22/11 mmHg vs 127/73 +/- 30/14 mmHg) correlated with the decrease in blood volume (mean blood pressure: r = 0.33). Plasma ET-1 increased from 1.29 +/- 0.47 pg/mL before to 1.46 +/- 0.56 pg/mL (reference range 0.3-0.9) at the end of hemodialysis (P < 0.05). This rise was more pronounced in patients with hypertension than in normotensive individuals (P < 0.05). The change in blood volume (r = 0.41) and blood pressure (mean blood pressure: r = 0.34) correlated with plasma ET-1 at the end of hemodialysis (P < 0.05). Plasma ET-1 was enhanced in hemodialysis patients compared to normal subjects. During the hemodialysis session an increase in ET-1 was encountered, which was more pronounced in hypertensive than in normotensive patients and paralleled the hemodynamic changes. Apart from pre-existing hypertension, further factors potentially influencing ET-1 include local endothelial injury (arteriovenous fistula) and generalized bioincompatibility reactions (e.g. foreign surface contact) occurring during hemodialysis.

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“…Verapamil has been shown to counteract the effects of ET on the heart but less so on the kidney in animal studies. 89,90 Nevertheless, verapamil and the dihydropyridine nifedipine constitute potent tools to inhibit endothelin-induced vasoconstriction. These are highly effective agents for abolishing the actions of an endothelin infusion on the kidney in healthy human volunteers, 57,91 as well as in patients with chronic hypertension.…”

Section: Endothelin and Diseasementioning

confidence: 99%