Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma concentrations of the recently isolated potent vasoconstrictory peptide endothelin were measured in 382 patients. The investigations were performed by means of a sensitive radioimmunoassay specific for Endothelin-1, 2. The results from 110 healthy volunteers displayed a normal range of 44.67 +/- 3.51 pg/ml. Significantly raised levels were found in 33 patients with chronic end-stage renal failure both before and after hemodialysis. In contrast, 35 patients with compensated renal insufficiency did not differ from the normals. Sixty-five patients after kidney transplantation revealed significantly elevated levels, as did 27 patients with acute myocardial infarction, 8 after coronary bypass surgery, and 5 with liver cirrhosis. The mean values of 27 patients with untreated hypertension, 22 with secondary hypertension, of various causes and 16 with coronary artery disease were comparable to the normal population. The values were significantly decreased in 9 pregnant women with hypertension and proteinuria. A marked decline was found in 5 patients with systemic lupus erythematodes, while 20 patients with rheumatoid arthritis demonstrated only a slight decrease. The pathophysiological role of endothelin as a local or circulating hormone in regulating systemic blood pressure or release of other hormones remains to be determined.
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PMID:[Plasma endothelin in normal probands and patients with nephrologic-rheumatologic and cardiovascular diseases]. 221 2

We investigated endothelin-1 mRNA expression in peripheral blood monocytes from 40 patients with IgA nephropathy, 40 with other glomerulonephritides and 10 with essential hypertension without renal diseases, and from 30 healthy age-matched controls. 95% of patients with IgA nephropathy had increased endothelin-1 mRNA expression in monocytes but little was detected from the other groups. Endothelin-1 mRNA was positively correlated with urinary protein excretion (95% CI 0.835-0.952) and histopathological findings (0.796-0.939). In 15 patients with IgA nephropathy endothelin-1 mRNA values and proteinuria decreased gradually after treatment. Endothelin-1 mRNA-expressing activated monocytes may be associated with the progression of IgA nephropathy.
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PMID:Endothelin-1 mRNA expression by peripheral blood monocytes in IgA nephropathy. 790 78

Endothelin (ET) is the most potent endogenous vasoconstrictory substance known. There are three structurally and pharmacologically separate endothelial isopeptides in humans; Endothelin-1 is exclusively produced in the vascular endothelium. It seems likely that ET acts as a local paracrine signal rather than a circulating hormone. The synthesis and release of ET is stimulated among others by hypoxia, thrombin and endotoxin. Its effects are mediated by specific, membrane-bound receptors, which are detectable in high concentrations in the fetoplacental tissue. ET-1 causes an initial transient fall in blood pressure, followed by a strong, long-lasting increase in peripheral resistance and blood pressure. Plasma ET-1 levels are increased in preeclampsia as compared to those of normal pregnancies, and do not correlate with mean arterial blood pressure and degree of proteinuria. In umbilical cord blood ET-1 concentrations are 2.5-10-fold higher than those of maternal plasma. Determination of plasma ET is unlikely to be of value in the prediction of the disease. ET-1 induces an increased synthesis of vasodilatory prostaglandins (PGI2, PGE2) and an increased production of endothelial-derived relaxing factor (EDRF); thromboxane concentrations in blood are elevated by thrombin-induced activation of platelets. In animal models ET-1 causes an activation of plasmatic coagulation with consecutive hypercoagulability. In preeclampsia ET may play an important role in the regulation of the endothelial balance. Future therapeutic approaches may include the development of effective ET-antibodies or of inhibitors of the endothelin-converting enzyme.
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PMID:[Endothelin--possible significance in pregnancy and hypertensive pregnancy]. 823 57

1. Glomerulosclerosis and tubulointerstitial damage are common histological abnormalities of many renal diseases that progress to end-stage renal failure. 2. In some models of renal damage, glomerulosclerosis seems to be associated with increased glomerular capillary pressure. 3. Due to the positive correlation of glomerulosclerosis and proteinuria in both experimental models and in humans, abnormal permeability to macromolecules has also been considered a possible determinant of glomerulosclerosis. 4. Abnormally filtered macromolecules have an intrinsic toxicity to the kidney due to protein over-reabsorption, possibly leading to tubulointerstitial damage. 5. Endothelin-1 (ET-1) is a vasoconstrictor peptide that induces mitogenesis and the accumulation of matrix proteins by mesangial cells. 6. Evidence is available that ET-1 plays a role in progressive renal disease in different experimental models, including renal mass reduction, lupus nephritis, streptozotocin-induced diabetes and puromycin-induced nephrosis.
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PMID:Endothelin is a key modulator of progressive renal injury: experimental data and novel therapeutic strategies. 871 73

Angiotensin-converting enzyme (ACE) inhibitors diminish proteinuria and the progression to renal failure in several experimental models of renal injury. Endothelin-1 (ET-1) possesses potent biological actions on renal vessels and has been considered as a potential mediator of renal damage. Because angiotensin II (Ang II) induces ET-1 synthesis in endothelial and mesangial cells, we hypothesized that some of the beneficial effects of the ACE inhibitors could result from the blockade of ET-1 synthesis. In a normotensive model of immune-complex nephritis, in which there exists an increase in renal ACE activity, the effect of the ACE inhibitor quinapril on preproET-1 and ETA receptor mRNA expression, as well as on ET-1 protein levels, was examined in this study. In relation to controls, nephritic rats showed an increase in preproET-1 and ETA receptor gene expression in renal cortex and medulla, coinciding with the maximal renal ACE activity. PreproET-1 mRNA (in situ hybridization) and ET-1 protein (immunohistochemistry) were localized in glomerular capillary walls, mesangial and glomerular epithelial cells, as well as in the brush border of some proximal tubules, and in small vessels. In nephritic rats, there was an increase in preproET-1 mRNA levels and ET-1 protein in all of these areas, without modification of their distribution. The administration of the ACE inhibitor quinapril decreased proteinuria and morphological lesions, preproET-1 gene transcription, and ET-1 protein levels, as well as the ETA receptor mRNA. The results from this study show that in a normotensive model of immune-complex nephritis, there was an overexpression of ET-1 in several structures of the kidney that was downregulated by quinapril administration. The beneficial effect of ACE inhibitors could be a result of the modulation of local production of Ang II and ET-1.
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PMID:Quinapril decreases renal endothelin-1 expression and synthesis in a normotensive model of immune-complex nephritis. 917 45

Previous studies showed a renoprotective effect of l-arginine in experimental uremia. Whether this was caused by an increased nitric oxide (NO) release or depended on l-arginine per se is not clear. Here, we evaluated whether chronic administration of an NO donor, molsidomine, controlled systemic blood pressure and renal disease progression and prolonged survival in rats with renal mass reduction (RMR). Rats with RMR received the following daily in the drinking water: group 1 (n = 21), no specific therapy (vehicle); group 2 (n = 12), molsidomine, 120 mg/L; group 3 (n = 9), lisinopril, 25 mg/L; and group 4 (n = 12), reserpine, 5 mg/L, hydralazine, 80 mg/L, and hydrochlorothiazide, 25 mg/L, from day 21 after surgery, when rats had hypertension and proteinuria, until the death of the vehicle-treated rats. Molsidomine normalized systemic hypertension, only partially reduced proteinuria and serum creatinine levels, but significantly prolonged animal survival, particularly in the early stage of the disease. Lisinopril at a similar systemic blood pressure was even better than molsidomine in limiting proteinuria, preserving renal function, and prolonging survival, but triple therapy, despite being effective on blood pressure, offered no renoprotection or prolonged survival. Endothelin-1 (ET-1) levels, formed in excessive amounts by the kidneys of these animals, were reduced by molsidomine and lisinopril, but not by triple therapy. The prolongation of survival by NO donor could be attributed to its effect of reducing ET levels, which in turn may limit the smooth muscle cell proliferation and matrix accumulation responsible for organ and, especially, myocardial fibrosis in uremia.
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PMID:Renoprotection by nitric oxide donor and lisinopril in the remnant kidney model. 1019 19

Chronic kidney diseases are increasing worldwide at an alarming rate, and they are emerging as a major public health problem. Treatments that slow the progression of chronic kidney disease are needed. Endothelin-1 (ET-1) is a potent vasoconstrictor with proinflammatory, mitogenic and profibrotic effects that is closely involved in both normal renal physiology and pathology. Increasing evidence suggests that ET-1 and its cognate receptors are involved in a variety of progressive renal disorders to the extent that renal ET-1 expression correlates with disease severity and renal function impairment. Endothelin receptor antagonists have been used in renoprotection studies owing to their capacity of improving renal hemodynamics and reducing proteinuria. Whether selective ET(A) or non-selective ET(A)/ET(B) receptor antagonists are preferable is still a matter of debate. As angiotensin II blockers are not invariably effective in retarding disease progression when treatment is started late in the course of the disease, it is foreseeable that an ET-1 antagonist in addition to angiotensin-converting enzyme inhibitors could represent a combined treatment for progressive nephropathies. The focus of this review is to examine the role endothelin-1 plays in kidney diseases and to determine the ideal setting for antagonizing its biological activity in chronic nephropathies.
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PMID:Endothelin receptor selectivity in chronic renal failure. 1933 45

Preeclampsia is a disorder of hypertension and proteinuria that affects 6 - 8% of normal pregnancies. Recent research has revealed many molecular mechanisms that may contribute to systemic endothelial dysfunction, glomerular capillary endotheliosis, dysregulation of the glomerular filtration apparatus, and podocyte loss. An ischemic placenta elaborates soluble FMS-like tyrosine kinase 1 (sFlt-1), a soluble receptor for vascular endothelial growth factor (VEGF). A variety of mediators, including nitric oxide, Angiotensin II receptor autoantibodies (AT1AA), and endothelin-1 may serve to maintain placental ischemia and systemic endothelial dysfunction. Endothelin-1 and decreased vascular endothelial growth factor may adversely affect overall expression and distribution of podocyte foot process proteins, leading to proteinuria. Podocyte derangements may lead to podocyte apoptosis and loss, as evidenced by the detection of live podocytes and podocyte products in the urine of preeclamptic women. In this review, we explore recent research elucidating the interactions of placenta, endothelium, and podocyte leading to the clinical syndrome of preeclampsia.
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PMID:From placenta to podocyte: vascular and podocyte pathophysiology in preeclampsia. 2287 14

The endothelin (ET) system seems to play a pivotal role in hypertension and in proteinuric kidney disease, including the micro- and macro-vascular complications of diabetes. Endothelin-1 (ET-1) is a multifunctional peptide that primarily acts as a potent vasoconstrictor with direct effects on systemic vasculature and the kidney. ET-1 and ET receptors are expressed in the vascular smooth muscle cells, endothelial cells, fibroblasts and macrophages in systemic vasculature and arterioles of the kidney, and are associated with collagen accumulation, inflammation, extracellular matrix remodeling, and renal fibrosis. Experimental evidence and recent clinical studies suggest that endothelin receptor blockade, in particular selective ETAR blockade, holds promise in the treatment of hypertension, proteinuria, and diabetes. Concomitant blockade of the ETB receptor is not usually beneficial and may lead to vasoconstriction and salt and water retention. The side-effect profile of ET receptor antagonists and relatively poor antagonist selectivity for ETA receptor are limitations that need to be addressed. This review will discuss what is currently known about the endothelin system, the role of ET-1 in the pathogenesis of hypertension and kidney disease, and summarize literature on the therapeutic potential of endothelin system antagonism.
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PMID:Endothelin antagonists in hypertension and kidney disease. 2307 Feb 75

The incidence and prevalence of chronic kidney disease (CKD), with diabetes and hypertension accounting for the majority of cases, is on the rise, with up to 160 million individuals worldwide predicted to be affected by 2020. Given that current treatment options, primarily targeted at the renin-angiotensin system, only modestly slow down progression to end-stage renal disease, the urgent need for additional effective therapeutics is evident. Endothelin-1 (ET-1), largely through activation of endothelin A receptors, has been strongly implicated in renal cell injury, proteinuria, inflammation, and fibrosis leading to CKD. Endothelin receptor antagonists (ERAs) have been demonstrated to ameliorate or even reverse renal injury and/or fibrosis in experimental models of CKD, whereas clinical trials indicate a substantial antiproteinuric effect of ERAs in diabetic and nondiabetic CKD patients even on top of maximal renin-angiotensin system blockade. This review summarizes the role of ET in CKD pathogenesis and discusses the potential therapeutic benefit of targeting the ET system in CKD, with attention to the risks and benefits of such an approach.
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PMID:Endothelin and endothelin antagonists in chronic kidney disease. 2480 8


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