Endothelin inhibits renin release from juxtaglomerular cells via endothelin receptors A and B via a transient receptor potential canonical-mediated pathway

Ortiz-Capisano, M. Cecilia

doi:10.14814/phy2.12240

Cited by 4 publications

(4 citation statements)

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“…Therefore the amount of renin is a limiting step during the production of Ang II, the main RAS component that acts as a critical element to the regulation of blood pressure and CKD pathogenesis. Renin release by JG cells is stimulated by cAMP and is inhibited by an increase in intracellular calcium levels (Ortiz-Capisano et al 2013) and endothelins in a calcium dependent way (Ortiz-Capisano et al 2014). cAMP is a second messenger used for the transduction of intracellular signals in diverse biological processes, having an important role in stimulating renin gene expression.…”

Section: Involvement Of Adenosine In Renal Vascular Tone Regulationmentioning

confidence: 99%

Adenosine contribution to normal renal physiology and chronic kidney disease

Oyarzún

Garrido

Alarcón

et al. 2017

Molecular Aspects of Medicine

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Adenosine is a nucleoside that is particularly interesting to many scientific and clinical communities as it has important physiological and pathophysiological roles in the kidney. The distribution of adenosine receptors has only recently been elucidated; therefore it is likely that more biological roles of this nucleoside will be unveiled in the near future. Since the discovery of the involvement of adenosine in renal vasoconstriction and regulation of local renin production, further evidence has shown that adenosine signaling is also involved in the tubuloglomerular feedback mechanism, sodium reabsorption and the adaptive response to acute insults, such as ischemia. However, the most interesting finding was the increased adenosine levels in chronic kidney diseases such as diabetic nephropathy and also in non-diabetic animal models of renal fibrosis. When adenosine is chronically increased its signaling via the adenosine receptors may change, switching to a state that induces renal damage and produces phenotypic changes in resident cells. This review discusses the physiological and pathophysiological roles of adenosine and pays special attention to the mechanisms associated with switching homeostatic nucleoside levels to increased adenosine production in kidneys affected by CKD.

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Section: Involvement Of Adenosine In Renal Vascular Tone Regulationmentioning

confidence: 99%

Adenosine contribution to normal renal physiology and chronic kidney disease

Oyarzún

Garrido

Alarcón

et al. 2017

Molecular Aspects of Medicine

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“…Importantly, multiple regression analysis revealed that ET-1 is not only an independent determinant of both the blood pressure rise and proteinuria in PE, but also a renin suppressor [Verdonk et al 2015]. Animal studies support the latter [Ritthaler et al 1995; Ortiz-Capisano, 2014].…”

Section: Endothelin-1 In Clinical Pre-eclampsiamentioning

confidence: 99%

The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia

Saleh

Verdonk

Visser

et al. 2016

Therapeutic Advances in Cardiovascular Disease

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Pre-eclampsia (PE) is the most frequently encountered medical complication during pregnancy. It is characterized by a rise in systemic vascular resistance with a relatively low cardiac output and hypovolemia, combined with severe proteinuria. Despite the hypovolemia, renin-angiotensin system (RAS) activity is suppressed and aldosterone levels are decreased to the same degree as renin. This suggests that the RAS is not the cause of the hypertension in PE, but rather that its suppression is the consequence of the rise in blood pressure. Abnormal placentation early in pregnancy is widely assumed to be an important initial event in the onset of PE. Eventually, this results in the release of anti-angiogenic factors [in particular, soluble Fms-like tyrosine kinase-1 (sFlt-1)] and cytokines, leading to generalized vascular dysfunction. Elevated sFlt-1 levels bind and inactivate vascular endothelial growth factor (VEGF). Of interest, VEGF inhibition with drugs like sunitinib, applied in cancer patients, results in a PE-like syndrome, characterized by hypertension, proteinuria and renal toxicity. Both in cancer patients treated with sunitinib and in pregnant women with PE, significant rises in endothelin-1 occur. Multiple regression analysis revealed that endothelin-1 is an independent determinant of the hypertension and proteinuria in PE, and additionally a renin suppressor. Moreover, studies in animal models representative of PE, have shown that endothelin receptor blockers prevent the development of this disease. Similarly, endothelin receptor blockers are protective during sunitinib treatment. Taken together, activation of the endothelin system emerges as an important pathway causing the clinical manifestations of PE. This paper critically addresses this concept, taking into consideration both clinical and preclinical data, and simultaneously discusses the therapeutic consequences of this observation.

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“…16,17 Moreover, ET-1 has been reported to suppress renin release in animal models. 18,19 The cause of the RAAS suppression in preeclampsia has always been elusive. Given the reduced circulating volume in preeclampsia, the opposite should have occurred.…”

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confidence: 99%

Association Studies Suggest a Key Role for Endothelin-1 in the Pathogenesis of Preeclampsia and the Accompanying Renin–Angiotensin–Aldosterone System Suppression

et al. 2015

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P reeclampsia is a pregnancy-related disorder, clinically characterized by the new onset of proteinuria and hypertension in the second half of pregnancy, with a great effect on maternal and fetal morbidity and mortality worldwide. 1A better understanding of the pathogenic mechanisms underlying preeclampsia might help identifying biomarkers that allow early diagnosis and treatment of preeclampsia. Recently, disturbances in angiogenic balance (favoring antiangiogenic over proangiogenic factors), elevated endothelin-1 (ET-1) levels, and a suppressed renin-angiotensin-aldosterone system (RAAS) have been reported. [2][3][4] As a consequence, the ratio of the antiangiogenic soluble Fms-like tyrosine kinase-1 (sFlt-1) and the proangiogenic placental growth factor (PlGF) is now thought to be a reliable biomarker for the diagnosis of preeclampsia. 5 In fact, patients with a ratio ≥85 have a poor pregnancy outcome independent of their clinical diagnosis compared with patients with a ratio <85. 5Of interest, treatment of cancer patients with antiangiogenic drugs (which, like sFlt-1, prevent the actions of vascular endothelial growth factor [VEGF]) resulted in hypertension, proteinuria, renin suppression, and elevated ET-1 levels. 6 Animal studies with antiangiogenic drugs additionally revealed that the renal histological changes observed during such treatment, in particular glomerular endotheliosis, resembled the renal alterations observed in preeclampsia. 7 From the observation that the dual ET A/B receptor antagonist macitentan prevented both the rise in blood pressure and proteinuria during Abstract-Women with preeclampsia display low renin-angiotensin-aldosterone system activity and a high antiangiogenic state, the latter characterized by high levels of soluble Fms-like tyrosine kinase (sFlt)-1 and reduced placental growth factor levels. To investigate whether renin-angiotensin-aldosterone system suppression in preeclampsia is because of this disturbed angiogenic balance, we measured mean arterial pressure, creatinine, endothelin-1 (ET-1), and reninangiotensin-aldosterone system components in pregnant women with a high (≥85; n=38) or low (<85; n=65) soluble Fms-like tyrosine kinase-1/placental growth factor ratio. Plasma ET-1 levels were increased in women with a high ratio, whereas their plasma renin activity and plasma concentrations of renin, angiotensinogen, and aldosterone were decreased. Plasma renin activity-aldosterone relationships were identical in both the groups. Multiple regression analysis revealed that plasma renin concentration correlated independently with mean arterial pressure and plasma ET-1. Plasma ET-1 correlated positively with soluble Fms-like tyrosine kinase-1 and negatively with plasma renin concentration, and urinary protein correlated with plasma ET-1 and mean arterial pressure. Despite the lower plasma levels of renin and angiotensinogen in the high-ratio group, their urinary levels of these components were elevated. Correction for albumin revealed that this was because of increased glomer...

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Endothelin inhibits renin release from juxtaglomerular cells via endothelin receptors A and B via a transient receptor potential canonical-mediated pathway

Cited by 4 publications

References 58 publications

Adenosine contribution to normal renal physiology and chronic kidney disease

Adenosine contribution to normal renal physiology and chronic kidney disease

The emerging role of endothelin-1 in the pathogenesis of pre-eclampsia

Association Studies Suggest a Key Role for Endothelin-1 in the Pathogenesis of Preeclampsia and the Accompanying Renin–Angiotensin–Aldosterone System Suppression

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