Significance of Endothelin Receptor Subtypes in the Kidneys of Spontaneously Hypertensive Rats

Hocher, Berthold; Rohmeiss, Peter; Zart, Rüdiger; Diekmann, Franziska; Vogt, Volker; Metz, Damien; Fakhuri, M.; Gretz, Norbert; Bauer, Christian; Koppenhagen, K; Distler, A.

doi:10.1097/00005344-199506263-00138

Cited by 18 publications

(7 citation statements)

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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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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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“…infusion of I mg/kg/h bosentan for the duration of the experiment. Bosentan is known to lower arterial blood pressure when given in higher doses than in the present study [4,10). The dose o f bosentan was chosen on the basis of pilot experiments showing that this dose had no effect on RPP.…”

Section: Experimental Protocolsmentioning

confidence: 49%

“…However, bosentan caused a small in- crease in renal vascular resistance and a decrease in RBF. The observed renal vasoconstriction has to be explained by a blockade of renal vascular ET-B receptors, as treatment of SHR with the selective ET-A-receptor antagonist, BQ123, results in renal vasodilatation with an increase in RBF and a decrease in renal vascular resistance [4], This concept is further supported by the observation that bosentan at a 'low er' dose range (as used in our study) preferentially blocks the effects of ET-1 on ET-B receptors [10. 18].…”

Section: Discussionmentioning

confidence: 99%

“…In support of this notion it was recently demonstrated by in situ hybridization and receptor autoradiography that spon taneously hypertensive rats (SHR) exhibit a pronounced upregulation of both the ET-A and ET-B receptors in the kid ney [4]. However, most of the data supporting an involve ment of ET in renal hemodynamics and sodium excretion are derived from experiments where ET or ET-receptor ago nists were given in rather pharmacological doses [1.…”

Section: Introductionmentioning

confidence: 99%

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Influence of the Renal Endothelin System on the Autoregulation of Renal Blood Flow in Spontaneously Hypertensive Rats

Braun

Lang

Hocher

et al. 1997

Kidney Blood Press Res

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The renal endothelin (ET) system has been claimed to play an important role in the regulation of renal blood flow (RBF) and sodium excretion in primary hypertension. The aim of the present study was to investigate the contribution of the endogenous ET system in the autoregulation of total RBF, cortical blood flow (CBF), pressure-dependent plasma renin activity (PRA) and pressure natriuresis in spontaneously hypertensive rats (SHR) by means of the combined (A/B) ET-receptor antagonist, bosentan. In anesthetized rats, RBF was measured by transit-time flow probes and CBF by laser flow probes. During the experiments, the rats received an intrarenal infusion of either bosentan (1 mg/kg/h) or vehicle. Renal perfusion pressure (RPP) was lowered in pressure steps of 5 mm Hg with a servo-controlled electropneumatic device via an inflatable suprarenal cuff. Bosentan had no effect on resting RPP, CBF, PRA and renal sodium excretion, whereas RBF was lowered by 30% (p < 0.05). Furthermore after bosentan the rats revealed a complete loss of RBF autoregulation. In contrast no changes in autoregulation of CBF, pressure-dependent PRA and pressure natriuresis were observed. Our findings demonstrate a significant impairment in total RBF autoregulatory ability during renal ET-receptor blockade which is not confined to the cortical vessels. These data suggest that the renal ET system plays an important role in the dynamic regulation of renal blood flow in SHR.

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“…Similarly, Hughes et al [47] demonstrated that isolated or cultured renal IMCD of spontaneously hypertensive rats contains lower ET-1 mRNA and releases less ET-1 compared to IMCD derived from Wistar-Kyoto controls. In contrast to ET-1, the status of ET A and ET B in the kidneys of hypertensive patients was not studied; however, in experimental models of hypertension, such as spontaneously hypertensive rats [48] , there is a remarkable upregulation of ET A and ET B in the renal tissue. In light of the regulatory role of the intrarenal ET system in renal hemodynamics and excretory function, the increased urinary excretion of the ET A and ET B receptors in hypertensive patients may represent a compensatory mechanism to counterbalance high BP.…”

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Endothelin Receptors ET<sub>A</sub> and ET<sub>B</sub> in Hypertensive Patients and Normotensive Subjects

Karram¹,

Khamaisi²,

Bishara³

et al. 2009

Kidney Blood Press Res

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Background/Aims: Endothelin (ET)-1 is produced by most renal cell types. Renal tubular and vascular cells express both the ET receptors ET_A and ET_B. Since significant amounts of ET-1 of renal origin were detected in human urine, urinary ET-1 has been used as an index for the capacity of renal ET-1 production. Here, we determine the existence of additional components of the intrarenal ET system, namely the ET_A and ET_B receptor subtypes, in the urine of normal and hypertensive subjects. Methods: ET_A and ET_B receptors were detected in urine samples that were concentrated by TCA precipitation, Speedvac or ProteoSpin™. Results: Analysis of the human urine extracts revealed the existence of approximately 50 and 55 kDa of immunoreactive proteins, corresponding to ET_B and ET_A, respectively, indicating that intact ET_A and ET_B are excreted in the urine of healthy subjects and hypertensive patients. Normotensive and hypertensive subjects had statistically comparable ET_B excretion normalized to creatinine (0.58 ± 0.16 vs. 0.83 ± 0.17 μg/mg creatinine, respectively; p = 0.304). In contrast, ET_A excretion was higher among hypertensive subjects (0.05 ± 0.01 vs. 0.11 ± 0.02 μg/mg creatinine; p = 0.0451). Immunostaining of ET_A and ET_B in the human urinary system revealed expression of both receptors, principally in tubular cells (mainly in medullary collecting ducts) and in the bladder urothelium, and ET_A expression in the peritubular capillaries and arterioles. Urinary ET receptors closely and inversely correlated with indices of urine concentration, suggesting that their shedding is principally affected by urine flow. Conclusion: ET receptors are present in human urine, conceivably originating within the urinary system. Their excretion is principally affected by urinary concentration. It remains to be determined whether urinary ET_A/ET_B is of physiological/pathophysiological relevance.

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Significance of Endothelin Receptor Subtypes in the Kidneys of Spontaneously Hypertensive Rats

Cited by 18 publications

References 0 publications

Working under pressure: the vascular endothelium in arterial hypertension

Working under pressure: the vascular endothelium in arterial hypertension

Influence of the Renal Endothelin System on the Autoregulation of Renal Blood Flow in Spontaneously Hypertensive Rats

Urinary Excretion of Endothelin Receptors ET<sub>A</sub> and ET<sub>B</sub> in Hypertensive Patients and Normotensive Subjects

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