Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy

Mattia, G. De; Cassone-Faldetta, M.; Bellini, Cesare; Bravi, M.; Laurenti, O.; Baldoncini, R.; Santucci, A.; Ferri, Claudio

doi:10.1016/s0895-7061(98)00094-6

Cited by 60 publications

(40 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Once again, there are few studies examining renal ET-1 in humans with diabetes. Raised 24-h urinary ET-1 was present in Type II diabetic patients with albuminuria [77] and increases in circulating ET-1 preceded the microalbuminuric phase of renal damage related to diabetes [78].…”

Section: In Vivo Haemodynamic Studiesmentioning

confidence: 93%

Endothelin: emerging role in diabetic vascular complications

1999

View full text Add to dashboard Cite

The endothelin (ET) family consists of three 21-amino acid peptides designated ET-1, 2]. The biological actions of the ETs are primarily mediated by two distinct, G-protein-coupled receptor subtypes designated ET A and ET B [2]. Endothelin A receptors have a higher affinity for ET-1 and ET-2 than ET-3 and the ET B receptor binds all three isoforms with equal affinity. Translation of preproET mRNA generates preproET, which is converted to big ET and finally cleaved by ET converting enzyme (ECE) to facilitate production of biologically active peptide. Endothelin-1 released by vascular endothelial cells exerts an autocrine influence by promoting vasodilatation, subsequent to activation of ET B receptors located on endothelial cells. It also exerts a paracrine effect on adjacent vascular smooth muscle cells (VSMC) in evoking vasoconstrictor and mitogenic actions by activation of both ET A and ET B receptors. The primary target of ET-1 is the vasculature where it evokes transient vasodilatation mediated by endothelial ET B receptors, followed by slow-onset and sustained contraction mediated by ET A and ET B receptors located on VSMC. The functional response to ET-1 varies throughout different tissues and vascular beds due to differences in distribution and expression of these two receptor subtypes. Endothelin-1 Diabetologia (1999) AbstractSince the discovery of endothelin-1 as the most potent endothelial-derived vasoconstrictor/mitogenic peptide a decade ago, considerable evidence has implicated this peptide in various cardiovascular disease states, including diabetes mellitus. Plasma and tissue concentrations of endothelin-1 as well as responses to the peptide are changed in various forms of the disease in humans and animals. Endothelin activity is also altered in atherosclerotic and ischaemic disease, nephropathy, retinopathy, erectile dysfunction, and neuropathy, many of the well-known complications of diabetes. Striking new evidence shows that antagonists of the endothelin system might beneficially affect and potentially overcome some of these complications. Despite this, lack of direct proof of causation makes this peptide's role in the disease uncertain. This review examines the current state of thought on the role of endothelin in diabetes and in the complications of the disease as well as the likely roles of altered metabolic variables in modulating endothelin-1 concentrations and its activity. It is concluded that although alterations in endothelin-1 release and action are clearly associated with the diabetic state, further studies using inhibitors of the endothelin system are warranted to determine its precise role in the complications of the disease. [Diabetologia (1999

show abstract

Section: In Vivo Haemodynamic Studiesmentioning

confidence: 93%

Endothelin: emerging role in diabetic vascular complications

1999

View full text Add to dashboard Cite

show abstract

“…Studies in animal models of diabetes mellitus have shown increased glomerular gene expression and urinary excretion of endothelin-1 [110, 111]. In addition, human studies [112, 113] have reported an increase in endothelin-1 levels in patients with type 2 diabetes mellitus or hypertension and microalbuminuria, suggesting an involvement of endothelin-1 in the development of nephropathy in these patients. Among various mechanisms implicated in endothelin-related renal injury is the stimulation of a protein kinase C regulated phospholipase D which hydrolyzes phospholipid substrates and induces generation of phosphatidic acids that stimulate proliferation in mesangial cells [114].…”

Section: Insulin and Endothelin-1mentioning

confidence: 99%

Insulin Resistance, Hyperinsulinemia, and Renal Injury: Mechanisms and Implications

Sarafidis¹,

Ruilope²

2006

Am J Nephrol

228

183

View full text Add to dashboard Cite

Most of the basic components of the metabolic syndrome, namely type 2 diabetes mellitus, hypertension, obesity, or low high-density lipoprotein cholesterol levels, apart from being major risk factors for cardiovascular disease have been also associated with an increased risk of chronic kidney disease. However, several epidemiologic studies conducted over the past years suggest that the central component of the syndrome, insulin resistance, as well as compensatory hyperinsulinemia are independently associated with an increased prevalence of chronic kidney disease. In addition, background studies support the existence of several pathways linking insulin resistance and hyperinsulinemia with kidney damage. Insulin per se promotes the proliferation of renal cells and stimulates the production of other important growth factors such as insulin-like growth factor-1 and transforming growth factor beta. Insulin also upregulates the expression of angiotensin II type 1 receptor in mesangial cells, thus enhancing the deleterious effects of angiotensin II in the kidney, and stimulates production and renal action of endothelin-1. Moreover, insulin resistance and hyperinsulinemia are associated with decreased endothelial production of nitric oxide and increased oxidative stress which have been also implicated in the progression of diabetic nephropathy. This review analyzes the above and other potential mechanisms, through which insulin resistance and hyperinsulinemia can contribute to renal injury.

show abstract

“…Alteration of ETs has been demonstrated in both type I and type II diabetes (Bertello et al, 1994;De Mattia et al, 1998;Donatelli et al, 1994;Haak et al, 1992;Kamoi et al, 1994;Kawamura et al, 1992;Laurenti et al, 1997;Letizia et al, 1997;Morise et al, 1995;Takahashi et al, 1990). Although, a number of studies can be cited that provide contradictory reports of plasma ET levels in diabetic patients, it should be noted that these peptides act in both an autocrine and paracrine fashion.…”

Section: Endothelins (Ets)mentioning

confidence: 99%

Growth Factors in Proliferative Diabetic Retinopathy

Khan

Chakrabarti

2003

Journal of Diabetes Research

View full text Add to dashboard Cite

Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients.

show abstract

Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy

Cited by 60 publications

References 21 publications

Endothelin: emerging role in diabetic vascular complications

Endothelin: emerging role in diabetic vascular complications

Insulin Resistance, Hyperinsulinemia, and Renal Injury: Mechanisms and Implications

Growth Factors in Proliferative Diabetic Retinopathy

Contact Info

Product

Resources

About