Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats

Hocher, Berthold; Rohmeiss, Peter; Zart, Rüdiger; Diekmann, Fritz; Vogt, Volker; Metz, Dieter; Fakhury, Myriam; Gretz, Norbert; Bauer, Christian; Koppenhagen, K; Neumayer, Hans H.; Distler, A.

doi:10.1016/s0008-6363(95)00200-6

Cited by 32 publications

(20 citation statements)

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“…These findings are in accordance with the results of functional studies (Lanese and Conger 1993;Wu et al 1997;Cavarape et al 1998) and with the detection of ET A receptor mRNA in all renal arteries (Hocher et al 1996). We can also confirm a weak signal for the ET B receptor in arterial endothelial cells.…”

Section: Et Receptors In Rat Kidneysupporting

confidence: 92%

“…We can also confirm a weak signal for the ET B receptor in arterial endothelial cells. Although neither Hocher et al (1996) nor Yamamoto and Uemura (1998) could detect ET B receptors on vascular smooth muscle cells by in situ hybridization and IHC, respectively, in our study ET B receptor immunoreactivity of smooth muscle cells was obvious in interlobular arteries as well as in afferent and efferent arterioles. These findings agree with previous functional studies demonstrating vasoconstriction of afferent and efferent arterioles by ET-1 being sensitive to ET A and ET B receptor antagonists (Endlich et al 1996;Hercule and Oyekan 2000a) and with the observation of ET-3-mediated decreases in renal cortical blood flow (Hercule and Oyekan 2000b).…”

Section: Et Receptors In Rat Kidneycontrasting

confidence: 86%

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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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Section: Et Receptors In Rat Kidneysupporting

confidence: 92%

Section: Et Receptors In Rat Kidneycontrasting

confidence: 86%

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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“…27 In SHR, uninephrectomy increases ET-1 gene expression and the amount of the corresponding peptide in mesangial cells, podocytes, and proximal tubules and vessels. 24 ET A and ET B receptors are overexpressed in the glomeruli of SHR, 11 and ET A receptors are overexpressed in vascular smooth muscle cells of intrarenal arteries also. 11 Furthermore, in SHR the receptor affinity for ET-1 is increased.…”

Section: Discussionmentioning

confidence: 96%

“…24 ET A and ET B receptors are overexpressed in the glomeruli of SHR, 11 and ET A receptors are overexpressed in vascular smooth muscle cells of intrarenal arteries also. 11 Furthermore, in SHR the receptor affinity for ET-1 is increased. 28 The inhibitory effect of ET A receptor blockade on the development of glomerulosclerosis and of interstitial or vascular lesions appears plausible in view of the known renal actions of ET-1, ie, mitogenic effects on mesangial cells 29,30 and increased expression of fibronectin and collagen.…”

Section: Discussionmentioning

confidence: 96%

Nephroprotection of an ET _A -Receptor Blocker (LU 135252) in Salt-Loaded Uninephrectomized Stroke-Prone Spontaneously Hypertensive Rats

et al. 1998

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Abstract-The present study was designed to assess whether the orally active and highly specific endothelin A (ET A ) receptor antagonist LU 135252 affects progressive renal dysfunction in a hypertensive rat model of renal damage, ie, the uninephrectomized (UNX) stroke-prone spontaneously hypertensive rat (SHRsp). The animals were examined on a normal salt (0.25%) diet and, to sensitize the kidney to hypertensive injury, also on a high salt (3%) diet. Stereological methods were used to quantify indices of glomerulosclerosis, vascular damage, and tubulointerstitial damage. Treatment with LU 135252 (100 mg/kg body wt) did not affect systolic blood pressure (BP) in animals on a normal salt diet during the whole period of the experiment (18 weeks) or in salt-loaded animals until week 10; subsequently, BP was slightly but significantly lower in salt-loaded UNX-SHRsp given LU 135252. Between weeks 6 and 12, 40% of the untreated UNX-SHRsp on a high salt diet, but none on a standard salt diet, died; such mortality was completely prevented by LU 135252. Indices of renal damage were more abnormal in salt-loaded UNX-SHRsp compared with UNX-SHRsp on a normal salt diet. Development of glomerulosclerosis and tubulointerstitial and vascular damage in UNX-SHRsp on high salt was completely prevented by LU 135252. The respective indices were no longer significantly different from those of salt-loaded sham-operated SHRsp controls. In the less severely damaged kidneys of UNX-SHRsp on normal salt, treatment with LU 135252 tended to ameliorate the indices, but the difference was not statistically significant. The results document a role of the ET system, specifically of ET A receptors, in the development of progressive renal injury in salt-loaded UNX-SHRsp. LU 135252 completely prevented death and renal damage resulting from salt loading.(Hypertension. 1998;31:995-1001.)

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“…176,177 The ET system is activated in several but not all animal models of arterial hypertension. 171,[178][179][180][181][182][183][184][185][186][187] Correspondingly, ET plasma levels have been reported to be elevated in certain patients with essential hypertension, 188 but this is a subject to controversy. 60,189 The causal role of ET-1 in the pathogenesis of hypertension thus remains unclear.…”

Section: Endothelin and Endothelin Antagonists In Hypertensionmentioning

confidence: 99%

Working under pressure: the vascular endothelium in arterial hypertension

et al. 2000

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The vascular endothelium synthesizes and releases a spectrum of vasoactive substances like nitric oxide (NO) and endothelin (ET). In hypertension, the delicate balance of endothelium-derived factors is disturbed. ET acts as the natural counterpart to endothelium-derived NO, which exerts vasodilating, antithrombotic, and antiproliferative effects, and inhibits leukocyte-adhesion to the vascular wall. Besides its blood pressure rising effect also in man, ET induces vascular and myocardial hypertrophy, which are independent risk factors for cardiovascular morbidity and mortality. The derangement of endothelial function in hypertension is likely to be caused in part by genetic factors, but also due to elevated blood pressure itself. Due to its position between blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both target and mediator of arterial hypertension. Oxi-

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Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats

Abstract: Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals.

Cited by 32 publications

References 20 publications

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

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

Nephroprotection of an ET _A -Receptor Blocker (LU 135252) in Salt-Loaded Uninephrectomized Stroke-Prone Spontaneously Hypertensive Rats

Working under pressure: the vascular endothelium in arterial hypertension

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Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats

Cited by 32 publications

References 20 publications

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

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

Nephroprotection of an ET A -Receptor Blocker (LU 135252) in Salt-Loaded Uninephrectomized Stroke-Prone Spontaneously Hypertensive Rats

Working under pressure: the vascular endothelium in arterial hypertension

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

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

Nephroprotection of an ET _A -Receptor Blocker (LU 135252) in Salt-Loaded Uninephrectomized Stroke-Prone Spontaneously Hypertensive Rats