Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats

Girchev, R; Bäcker, Angela; Markova, P.; Kramer, Herbert J.

doi:10.1111/j.1523-1755.2004.00483.x

Cited by 20 publications

(14 citation statements)

References 43 publications

(41 reference statements)

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“…The effects of bosentan are in agreement with our previous findings in SHR showing that bilateral renal denervation modulated the response to the ET A receptor antagonist BQ-123 [13] . From these results we suggest that an inadequate ET-1 synthesis and a reduced ET receptor number in the renal papilla of SHR in the presence of increased ERSNA [7] contributes to enhanced renal sodium retention in young [35] and adult [36] SHR and may thereby play a crucial role in the pathogenesis of hypertension in this genetic model.…”

Section: Discussionsupporting

confidence: 82%

“…In contrast, confirming our previous findings [13] and those of others [24] , we found that ET-1 content and prepro-ET-1 mRNA in the renal papilla are significantly lower in SHR than in WKY rats. These findings suggest an intrinsic defect in the renal ET system in SHR and are further supported by the observations that urinary ET excretion is lower in SHR compared to WKY rats [24] and that recipients of an SHR kidney exhibit a lower rate of urinary ET excretion than recipients of a kidney from WKY rats [5] .…”

Section: Discussioncontrasting

confidence: 56%

“…Thus, the renal functional alterations in SHR may be related to an altered intrarenal ET activity, which by itself or by interacting with renal nerves could lead to an abnormal control of body fluid volume and thereby contribute to the development of hypertension. Reduced renal papillary ET-1 content in SHR has been observed previously [13,16] and may already appear in early stages of the development of hypertension [24] .…”

Section: Discussionmentioning

confidence: 99%

“…Because of controversial interpretation of experimental data regarding the role of the tissue ET system in SHR and its possible contribution to the pathogenesis of spontaneous hypertension [13] , we investigated first, prepro-ET-1 mRNA, ET-1 concentration as well as density and affinity of ET receptors in renal cortical and papillary tissue and, second, the effects of bilateral renal denervation on these components of the renal ET system in SHR as compared to normotensive Wistar-Kyoto (WKY) rats. Third, we evaluated the effects of ET A/B receptor blockade on renal function in intact and renal denervated SHR and WKY rats to identify the functional contribution of the renal ET system and of its interaction with renal nerves to the regulation of renal excretory function in this model of genetic hypertension.…”

Section: Background and Methodsmentioning

confidence: 99%

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Interaction of Endothelin with Renal Nerves Modulates Kidney Function in Spontaneously Hypertensive Rats

Girchev

Bäcker

Markova

et al. 2006

Kidney Blood Press Res

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Background and Methods: We investigated kidney function, renal endothelin-1 concentration, prepro-endothelin-1 mRNA as well as endothelin receptor A and B mRNA expression and receptor properties in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with intact renal nerves and 7 days after renal denervation. In addition, responses of renal function to the non-selective ET_A/ET_B receptor blocker bosentan (10 mg/kg i.v. bolus injection) were studied. Results: In SHR, renal papillary prepro-endothelin-1 mRNA expression, endothelin-1 tissue concentrations and endothelin receptor density were significantly lower than in normotensive rats. Renal denervation was associated with a decrease in papillary tissue prepro-endothelin-1 mRNA and in WKY rats also with a significant reduction in papillary endothelin-1 content without affecting ET receptor density. Bosentan did not alter renal blood flow or glomerular filtration rate but decreased urine flow rate in both intact normotensive and hypertensive rats, whereas it decreased urine sodium and potassium excretion only in intact WKY. Bosentan had no effects on renal function in renal denervated rats. Conclusion: Since renal papillary endothelin-1 appears to counteract the fluid and sodium retaining effects of renal nerve activity, an impaired renal endothelin-1 synthesis in SHR may contribute to excessive sodium retention and thus to the pathogenesis of hypertension in SHR.

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Section: Discussionsupporting

confidence: 82%

Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Background and Methodsmentioning

confidence: 99%

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Interaction of Endothelin with Renal Nerves Modulates Kidney Function in Spontaneously Hypertensive Rats

Girchev

Bäcker

Markova

et al. 2006

Kidney Blood Press Res

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“…Patients with hypertension, in particular those with salt-sensitive hypertension, were found to excrete less ET-1 in their urine than normotensive subjects, indicating reduced renal ET-1 production in the hypertensive subjects (119). Reduced production of ET-1 in the renal medulla has also been found in some animal models of hypertension (120,121). Underlining the importance of the intrarenal endothelin system in the control of blood pressure and sodium and water homeostasis, mice with collecting duct-specific knockout of the ET-1 gene are hypertensive on a normal salt diet, and this hypertension is exacerbated by exposure to a high salt diet (43).…”

Section: Essential Hypertensionmentioning

confidence: 99%

Contrasting Actions of Endothelin ET_Aand ET_BReceptors in Cardiovascular Disease

Schneider

Boesen

Pollock

2007

Annu. Rev. Pharmacol. Toxicol.

262

247

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First identified as a powerful vasoconstrictor, endothelin has an extremely diverse set of actions that influence homeostatic mechanisms throughout the body. Two receptor subtypes, ET A and ET B , which usually have opposing actions, mediate the actions of endothelin. ET A receptors function to promote vasoconstriction, growth, and inflammation while ET B receptors produce vasodilation, increases in sodium excretion, and inhibit growth and inflammation. Potent and selective receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure and atherosclerosis. However, results are often contradictory and complicated because of the tissue-specific vasoconstrictor actions of ET B receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo. Considerable questions remain regarding whether ET A selective or non-selective ET A /ET B receptor antagonists would be useful in a range of clinical settings. Keywordsreceptor localization; pulmonary hypertension; heart failure; chronic kidney disease Shortly after it was discovered that the vascular endothelium releases a peptide capable of profound vasoconstriction, a considerable amount of attention was paid to the potential actions of endothelin in the pathogenesis of cardiovascular disease. We have since learned a great deal about how this paracrine factor influences function in an extremely wide range of areas including neurotransmission, cell growth and epithelial transport, just to name a few. This myriad of activities has allowed the endothelin system to garner a tremendous amount of attention from the pharmaceutical industry with the development of numerous receptor specific and non-specific antagonists as well as efforts to identify drugs that inhibit endothelin synthesis. This work has led to new therapeutic approaches to pulmonary arterial hypertension and most likely other diseases in the not too distant future. In addition to this enormous drug discovery effort, it has also become clear that endothelin plays an important physiological role in maintaining blood pressure homeostasis, for example, by facilitating the excretion of a high salt diet. Because of the almost bewildering range of actions of the endothelin peptides, we limit this review to focus on the receptor-specific cardiovascular actions of endothelin. ENDOTHELIN PEPTIDESEndothelin-1, a 21-amino-acid long peptide first isolated from the supernatant of cultured endothelial cells, is perhaps the most potent vasoconstrictor substance known (1). The human Address for Correspondence: David M. Pollock, Ph.D., Vascular Biology Center, Medical College of Georgia, 1459 Laney Walker Blvd., Augusta, GA 30912-2500, +1-706-721-8517 office, +1-706-721-9799 fax, dpollock@mcg.edu. NIH Public Access Author ManuscriptAnnu Rev Pharmacol Toxicol. Author manuscript; available in PMC 2010 February 22. P...

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Physiology of Endothelin and the Kidney

Kohan

Inscho

Wesson

et al. 2011

Comprehensive Physiology

104

136

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Since its discovery in 1988 as an endothelial cell-derived peptide that exerts the most potent vasoconstriction of any known endogenous compound, endothelin (ET) has emerged as an important regulator of renal physiology and pathophysiology. This review focuses on how the ET system impacts renal function in health; it is apparent that ET regulates multiple aspects of kidney function. These include modulation of glomerular filtration rate and renal blood flow, control of renin release, and regulation of transport of sodium, water, protons and bicarbonate. These effects are exerted through ET interactions with almost every cell type in the kidney, including mesangial cells, podocytes, endothelium, vascular smooth muscle, every section of the nephron, and renal nerves. In addition, while not the subject of the current review, ET can also indirectly affect renal function through modulation of extrarenal systems, including the vasculature, nervous system, adrenal gland, circulating hormones and the heart. As will become apparent, these pleiotropic effects of ET are of fundamental physiologic importance in the control of renal function in health. In addition, to help put these effects into perspective, we will also discuss, albeit to a relatively limited extent, how alterations in the ET system can contribute to hypertension and kidney disease.

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Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats

Cited by 20 publications

References 43 publications

Interaction of Endothelin with Renal Nerves Modulates Kidney Function in Spontaneously Hypertensive Rats

Interaction of Endothelin with Renal Nerves Modulates Kidney Function in Spontaneously Hypertensive Rats

Contrasting Actions of Endothelin ET_Aand ET_BReceptors in Cardiovascular Disease

Physiology of Endothelin and the Kidney

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Impaired response of the denervated kidney to endothelin receptor blockade in normotensive and spontaneously hypertensive rats

Cited by 20 publications

References 43 publications

Interaction of Endothelin with Renal Nerves Modulates Kidney Function in Spontaneously Hypertensive Rats

Interaction of Endothelin with Renal Nerves Modulates Kidney Function in Spontaneously Hypertensive Rats

Contrasting Actions of Endothelin ETAand ETBReceptors in Cardiovascular Disease

Physiology of Endothelin and the Kidney

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Product

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Contrasting Actions of Endothelin ET_Aand ET_BReceptors in Cardiovascular Disease