Evidence from receptor antagonists of an important role for ET<sub>B</sub> receptor‐mediated vasoconstrictor effects of endothelin‐1 in the rat kidney

Wellings, Robert; Corder, Roger; Warner, Timothy D.; Cristol, Jean‐Paul; Thiemermann, Christoph; Vane, John R.

doi:10.1111/j.1476-5381.1994.tb14767.x

Cited by 59 publications

(39 citation statements)

References 30 publications

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“…ET B receptors in vascular tissue have previously been linked to NO-mediated vasodilatory responses, which counteract ET A receptor-mediated vasoconstriction. 34 Hence, downregulation of ET B receptors as observed in the present study may contribute to the reduced endothelium-dependent relaxation to acetylcholine and may enhance ET contractions by allowing unopposed action of the peptide at vasoconstrictor ET A receptors. Indeed, in the present study, ET A receptor antagonism normalized vascular eNOS protein expression and nitrate levels.…”

Section: Discussionsupporting

confidence: 49%

Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11β-Hydroxysteroid Dehydrogenase Inhibition

Ruschitzka¹,

Quaschning²,

Noll³

et al. 2001

Circulation

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Background-The enzyme 11␤-hydroxysteroid dehydrogenase (11␤-HSD) prevents inappropriate activation of the nonselective mineralocorticoid receptors by glucocorticoids. Renal activity of 11␤-HSD is decreased in patients with apparent mineralocorticoid excess (SAME), licorice-induced hypertension, and essential hypertension. Although expressed in vascular cells, the role of 11␤-HSD in the regulation of vascular tone remains to be determined. Methods and Results-Glycyrrhizic acid (GA; 50 mg/kg IP, twice daily for 7 days) caused a significant inhibition of 11␤-HSD activity and induced hypertension in Wistar-Kyoto rats (157 versus 127 mm Hg in controls; PϽ0.01). After 11␤-HSD inhibition, aortic endothelial nitric oxide (NO) synthase (eNOS) protein content, nitrate tissue levels, and acetylcholine-induced release of NO were blunted (all PϽ0.05 versus controls). In contrast, vascular prepro-endothelin (ET)-1 gene expression, ET-1 protein levels, and vascular reactivity to ET-1 were enhanced by GA treatment (PϽ0.05 versus controls). Chronic ET A receptor blockade with LU135252 (50 mg · kg Ϫ1 · d Ϫ1 ) normalized blood pressure, ET-1 tissue content, vascular reactivity to ET-1, vascular eNOS protein content, and nitrate tissue levels and improved NO-mediated endothelial function in GA-treated rats (PϽ0.05 to 0.01 versus untreated and verapamil-treated controls). In human endothelial cells, GA increased production of ET-1 in the presence of corticosterone, which indicates that activation of the vascular ET-1 system by 11␤-HSD inhibition can occur independently of changes in blood pressure but is dependent on the presence of glucocorticoids. Conclusions-Chronic

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Section: Discussionsupporting

confidence: 49%

Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11β-Hydroxysteroid Dehydrogenase Inhibition

Ruschitzka¹,

Quaschning²,

Noll³

et al. 2001

Circulation

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“…In rats for example, the renal vasculature expresses contractile ETB receptors (Cristol et al, 1993;Wellings et al, 1994) whilst human renal vessels express mainly the ETA subtype (Karet et al, 1993;Maguire et al, 1994b). ETBmediated constriction has been demonstrated in vascular smooth muscle from a variety of sources including rabbit jugular vein (Sumner et al, 1992) and in the rat in vivo (Gardiner et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Endothelin receptors in human coronary artery and aorta

Bacon

Davenport

1996

British J Pharmacology

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“…ET B receptor stimulation has been coupled to the release of nitric oxide (NO) and prostacyclin (Hyslop and de Nucci 1992), leading to vasodilation. In addition, presence of ET B receptors on vascular smooth muscle cells has been observed in different vascular beds (Wendel-Wellner et al 2002;Wendel et al 2005), and the ET B receptor subtype was considered to be the main receptor mediating ET-1-induced renal vasoconstriction in the rat (Wellings et al 1994;Endlich et al 1996). …”

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confidence: 99%

Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney

Wendel

Knels

Kummer

et al. 2006

J Histochem Cytochem.

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(WK) S U M M A R Y The endothelin (ET) receptor system is markedly involved in the regulation of renal function under both physiological and pathophysiological conditions. The present study determined the detailed cellular localization of both ET receptor subtypes, ET A and ET B , in the vascular and tubular system of the rat kidney by immunofluorescence microscopy. In the vascular system we observed both ET A and ET B receptors in the media of interlobular arteries and afferent and efferent arterioles. In interlobar and arcuate arteries, only ET A receptors were present on vascular smooth muscle cells. ET B receptor immunoreactivity was sparse on endothelial cells of renal arteries, whereas there was strong labeling of peritubular and glomerular capillaries as well as vasa recta endothelium. ET A receptors were evident on glomerular mesangial cells and pericytes of descending vasa recta bundles. In the renal tubular system, ET B receptors were located in epithelial cells of proximal tubules and inner medullary collecting ducts, whereas ET A receptors were found in distal tubules and cortical collecting ducts. Distribution of ET A and ET B receptors in the vascular and tubular system of the rat kidney reported in the present study supports the concept that both ET receptor subtypes cooperate in mediating renal cortical vasoconstriction but exert differential and partially antagonistic effects on renal medullary function.

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Evidence from receptor antagonists of an important role for ET_B receptor‐mediated vasoconstrictor effects of endothelin‐1 in the rat kidney

Abstract: 1 To characterize the receptor subtype(s) mediating the renal vasoconstrictor effects of the endothelin (ET) and sarafotoxin (SX) peptides in the isolated perfused kidney of the rat, we have examined the effects of endothelin-1 (ET-1), sarafotoxin 6b (SX6b) and sarafotoxin 6c (SX6c)

Cited by 59 publications

References 30 publications

Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11β-Hydroxysteroid Dehydrogenase Inhibition

Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11β-Hydroxysteroid Dehydrogenase Inhibition

Endothelin receptors in human coronary artery and aorta

Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney

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Evidence from receptor antagonists of an important role for ETB receptor‐mediated vasoconstrictor effects of endothelin‐1 in the rat kidney

Abstract: 1 To characterize the receptor subtype(s) mediating the renal vasoconstrictor effects of the endothelin (ET) and sarafotoxin (SX) peptides in the isolated perfused kidney of the rat, we have examined the effects of endothelin-1 (ET-1), sarafotoxin 6b (SX6b) and sarafotoxin 6c (SX6c)

Cited by 59 publications

References 30 publications

Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11β-Hydroxysteroid Dehydrogenase Inhibition

Endothelin 1 Type A Receptor Antagonism Prevents Vascular Dysfunction and Hypertension Induced by 11β-Hydroxysteroid Dehydrogenase Inhibition

Endothelin receptors in human coronary artery and aorta

Distribution of Endothelin Receptor Subtypes ETA and ETB in the Rat Kidney

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Evidence from receptor antagonists of an important role for ET_B receptor‐mediated vasoconstrictor effects of endothelin‐1 in the rat kidney

Distribution of Endothelin Receptor Subtypes ET_A and ET_B in the Rat Kidney