Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0730345 (microalbuminuria)
 4,018 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies have shown that both in hypertensives and in offspring of hypertensive parents there exists an altered renal functional reserve (RFR). The aim of this research was to study the RFR in newly diagnosed essential hypertensives, and to evaluate if any influences are played on RFR by circulating renin-angiotensin-aldosterone system, catecholamines, and plasma endothelin-1. In 16 essential hypertensives (EH) and in 10 healthy controls (C), on the 24-hour urine collection and on urine specimens taken after both an oral water load and an amino acids (AAs) infusion (4.16 ml/min for two hours), Ccr, microalbuminuria (AER) and its fractional clearance, and sodium excretion (Nau) were evaluated. Furthermore, both in basal condition and after the AAs load, blood samples were obtained to assay plasma renin activity (PRA) and aldosterone concentrations (PAC), circulating norepinephrine (NE) and endothelin-1 (ET-1). The C-group showed a mean increase in Ccr of 35%. No significant modifications in AER and in circulating hormones were observed. Among the 16 EH, thirteen subjects showed a significant increase in Ccr after the AAs load, with a mean increase of 32.5%. In the whole group of EH there were no significant differences in AER when comparing basal with after-load values, and Nau resulted significantly decreased after AAs infusion. The analysis of the hormonal pattern pointed out not significant changes in the behaviour of PRA, NE and ET-1, while a significant decrease in PAC was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The renal functional reserve in recently diagnosed essential hypertension. 802 14

Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD) in insulin-dependent diabetes mellitus (IDDM) patients, but the pathophysiological basis of this association is not clear. To see whether or not hemostatic dysfunctions might contribute to explain this association, we measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), factor VII activity, plasma fibrinogen, and plasma endothelin-1 (ET-1) in 13 microalbuminuric (albumin excretion rate [AER], 20-200 micrograms/min) and in 13 comparable normoalbuminuric (< 20 micrograms/min) IDDM patients. t-PA and ET-1 were similar in the two groups, whereas PAI-1 activity (5.65 +/- 1.92 vs. 0.85 +/- 0.58 IU/ml, P < 0.05), factor VII (87.85 +/- 4.94 vs. 76.54 +/- 2.31%, P < 0.05), and plasma fibrinogen (3.38 +/- 0.21 vs. 2.65 +/- 0.13 g/l, P < 0.05) were significantly higher in microalbuminuric than in normoalbuminuric patients. Plasma fibrinogen was related to AER (r2 = 0.23, P < 0.05), whereas triglycerides and factor VII were related to PAI-1 (r2 = 0.39, P < 0.001 and r2 = 0.10, P < 0.05). These results suggest that microalbuminuria is associated with a hypercoagulative and hypofibrinolytic state. Hemostatic dysfunctions might be a pathogenetic link between microalbuminuria and CVD.
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PMID:PAI-1 and factor VII activity are higher in IDDM patients with microalbuminuria. 831 15

The high incidence of cardiovascular morbidity and mortality in non-insulin-dependent diabetes mellitus with albuminuria cannot be fully explained by the presence of standard cardiovascular risk factors. We assessed some pathogenic factors of diabetic vascular atherosclerotic damage in 72 non-insulin-dependent diabetes mellitus patients controlled by diet alone and 60 healthy controls. Our study aim was to assess the early onset of these alterations and to correlate them with the presence of microalbuminuria. We determined their incidence in two carefully selected groups of diabetic patients without clinical signs of cardiovascular risk and complications, where diet alone achieved glycometabolic balance. Microalbuminuric patients had an alterated oxide-reductive balance and elevated values of plasminogen activator inhibitor, tissue plasminogen activator, von Willebrand factor, endothelin-1 and betathromboglobulin compared with the normoalbuminuric diabetics and controls. Our findings support the hypothesis that a state of endothelial dysfunction characterized by altered oxide-reductive balance, modified hemostasis and changes in the endothelial barrier properties occurs much earlier in non-insulin-dependent diabetic patient especially in diabetics with microalbuminuria. In addition, alterations in the oxide-reductive balance, and hemostasis occur early and may be an underlying cause of microangiopathic complications in microalbuminuric diabetics.
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PMID:Early endothelial alterations in non-insulin-dependent diabetes mellitus. 968 51

To evaluate the role of circulating and renal endothelin-1 (ET-1) in early diabetic nephropathy, plasma ET-1 levels and urinary ET-1 excretion were evaluated in lean, normotensive patients affected by non-insulin-dependent diabetes (NIDDM) either with (n = 9, NIDDM+) or without microalbuminuria (n = 18, NIDDM-); in never-treated, lean, essential hypertensive patients with (n = 12, EH+) or without microalbuminuria (n = 10, EH-); and in healthy volunteers (n = 12). Results showed higher plasma ET-1 levels in NIDDM+ (1.97 +/- 0.58 pg/mL) than in NIDDM- (1.59 +/- 0.14 pg/mL, P = .013), EH+ (1.40 +/- 0.21 pg/mL, P = .005), EH- (0.91 +/- 0.19 pg/mL, P < .0001), and controls (0.60 +/- 0.10 pg/mL, P < .0001). The circulating ET-1 concentration was also higher in EH+ than EH- and controls (P < .0001). Urinary ET-1 excretion did not differ (P = .387, NS) between NIDDM+ (48.5 +/- 20.1 pg/min) and NIDDM- (40.9 +/- 21.6 pg/min), but was significantly reduced (P < .0001) in both groups compared with controls (70.0 +/- 15.5 pg/min). Similar findings were observed in hypertensive subgroups. No correlations were found between urinary ET-1 and other variables, including plasma ET-1 levels, in all groups. In conclusion, NIDDM+ is accompanied by a significant increase in plasma ET-1 levels. A significant elevation of circulating ET-1 concentration was evident also in NIDDM-, suggesting that early abnormalities of ET-1 production might precede the microalbuminuric phase of diabetes-related renal damage.
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PMID:Role of plasma and urinary endothelin-1 in early diabetic and hypertensive nephropathy. 971 92

A connection between salt sensitivity and hypertension seems certain, but a number of issues remain unresolved, e.g., the mechanisms involved in salt sensitivity, its role in pathogenesis and/or maintenance of hypertension, and its ability to predict cardiorenal risk. The role of nitric oxide (NO) has been studied extensively. Evidence shows that NO, along with the vasoactive substances angiotensin II and endothelin-1, is important in modulating vascular tone. In addition, imbalances among these substances may participate in the abnormal cardiovascular and renal remodeling that occurs in hypertension. What causes such imbalances remains unclear. Animal studies show that in salt-sensitive subjects, the activity of NO synthase (NOS) fails to upregulate in response to increases in blood pressure, but that such activity upregulates rapidly in similar circumstances in non-salt-sensitive subjects. Human studies of essential hypertensives have shown an association between salt sensitivity and a number of conditions, including impaired endothelium-dependent relaxation mediated by NO, insulin resistance, microalbuminuria, and ventricular hypertrophy and cardiovascular events. These findings have intriguing implications in regard to whether, in hypertension, salt sensitivity might be a marker of increased cardiovascular and renal risk that is linked to abnormalities in the bioactivity of NO.
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PMID:Nitric oxide, salt sensitivity, and cardiorenal injury in hypertension. 1022 36

It is unknown whether and to what extent changes in various endothelial functions and adrenergic responsiveness are related to the development of microvascular complications in type 1 diabetes. Therefore, endothelium-dependent and endothelium-independent vasodilatation, endothelium-dependent hemostatic factors, and one and two adrenergic vasoconstrictor responses were determined in type 1 patients with and without microvascular complications. A total of 34 patients with type 1 diabetes were studied under euglycemic conditions on two occasions (11 without microangiopathy, 10 with proliferative and preproliferative retinopathy previously treated by laser coagulation, 13 with microalbuminuria, and 12 healthy volunteers also were studied). Forearm vascular responses to brachial artery infusions of N(G)-monomethyl-L-arginine (L-NMMA), sodium nitroprusside, acetylcholine (ACh), clonidine, and phenylephrine were determined. The ACh infusions were repeated during coinfusion of L-arginine. Furthermore, plasminogen activator inhibitor type 1 (PAI-1) activity, tissue plasminogen activator antigen levels, von Willebrand factor antigen levels, tissue factor pathway inhibitor (TFPI) activity, and endothelin-1 levels were measured. No differences in endothelium-dependent or endothelium-independent vasodilatation or adrenergic constriction were observed between the diabetic patients and the healthy volunteers. In comparison to the first ACh infusion, the maximal response to repeated ACh during L-arginine administration was reduced in the diabetic patients, except in the patients with proliferative and preproliferative retinopathy previously treated by laser coagulation. In these patients, the combined infusion of L-arginine and ACh resulted in an enhanced response. TFPI activity was elevated, and PAI-1 activity was reduced in the type 1 diabetic patients. Furthermore, PAI-1 activity was positively correlated with urinary albumin excretion (r = 0.48, P < 0.01) and inversely correlated with the vasodilatory response to the highest ACh dose (r = -0.37, P < 0.05). The response to the highest ACh and L-NMMA dose were positively correlated with mean arterial blood pressure (r = 0.32, P < 0.01; r = 0.41, P < 0.01, respectively). Forearm endothelium-dependent and endothelium-independent vasodilatation and adrenergic responsiveness were unaltered in type 1 diabetic patients with and without microvascular complications. Relative to healthy control subjects, endothelium-dependent vasodilatation was depressed during a repeated ACh challenge (with L-arginine coinfusion) in the diabetic patients without complications or with microalbuminuria. In contrast, this vasodilatation was enhanced in the patients with retinopathy. Elevation of TFPI was the most consistent marker of endothelial damage of all the endothelial markers measured.
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PMID:Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions. 1034 20

Previous evidence has demonstrated a relationship between growth factors and cardiovascular diseases. This study was aimed at evaluating levels of some endothelium-derived growth factors, and their relationship with microalbuminuria (MAU), in essential hypertension. Ninety-nine mild-moderate essential hypertensives (EH) and 25 healthy controls were studied. All patients underwent 24-h blood pressure monitoring, serum endothelin-1 (ET-1), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), and 24-h MAU assays. Later, EH were divided into two subsets consisting of microalbuminurics (MAU >11 microg/min) and nonmicroalbuminurics (MAU <11 microg/min). In microalbuminuric EH, circulating ET-1, bFGF, and PDGF were significantly higher than in nonmicroalbuminurics (P < .0001, P < .0001, P < .005, respectively) or in controls. In the group of 99 EH, significant positive correlations of MAU with both ET-1 and bFGF (r = 0.35, P < .001, and r = 0.34, P < .001, respectively) were found. ET-1 and bFGF correlated significantly (r = 0.31, P < .002). Circulating bFGF also correlated significantly with MAU in the microalbuminuric EH subset (r = 0.49, P < .01). Our results show that in microalbuminuric EH circulating levels of certain growth factors are increased. In human essential hypertension these factors are linked with MAU, an early cardiovascular and renal damage marker.
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PMID:Endothelium-derived factors in microalbuminuric and nonmicroalbuminuric essential hypertensives. 1070 17

In essential hypertensive subjects, acute and chronic administration of losartan was followed by favorable neurohormonal (norepinephrine, endothelin-1) and metabolic changes (microalbuminuria).
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PMID:Changes in plasma norepinephrine and endothelin levels and metabolic profile after AT1-receptor blockade in human hypertension. 1078 70

Adrenomedullin (ADM) infusion increases salt excretion in the rat. However, there is no evidence that this substance is related to changes in salt intake in humans. In this study we sought whether the urinary excretion rate of this autacoid is related to salt intake and by the expected changes in arterial pressure in patients with mild essential hypertension. The influence of salt intake on the renal excretion of ADM was investigated in 55 hypertensive patients in a double blind, randomized and crossover study comparing a 2-week 50 mmol/day salt intake period with a 150 mmol/day salt intake period. Twenty-four-hour ADM and endothelin-1 (ET-1) excretion rate were measured by radioimmunoassay on preextracted urinary samples (intraassay confidence variable <8%). The antibodies used in these assays had minimal ADM-ET-1 cross-reactivity (<1%). Twenty-four-hour microalbuminuria was measured by nephelometry. On univariate analysis changes in urinary ADM were significantly related to those in salt excretion (r = 0.33, P = .01) as well as to changes in urinary ET-1 (r = 0.56, P = .0001). Furthermore, changes in urinary albumin excretion were related to those in urinary ET-1 (r = 0.26, P = .05), but were independent of those in urinary ADM (P = .19). In a multiple regression model including age, sex, body mass index, and changes in systolic pressure, plasma renin activity and plasma aldosterone and urine volume, salt excretion resulted as the stronger independent predictor of urinary ADM (r = 0.33, P = .01). However, changes in urinary salt lost prediction power (P = .11) for urinary ADM when urinary ET-1 was introduced into the model. In this model (multiple r = 0.31) urinary ET-1 resulted to be the only independent predictor of urinary ADM (beta = 0.56, P = .0001). This study is the first to show that the renal excretion of ADM is related to changes in salt intake and that it is tightly linked to that of ET-1. The data support the notion that these autacoids play a role in the regulation of sodium metabolism in patients with mild hypertension. The intercorrelations between ET-1, ADM, and microalbuminuria are compatible with the hypothesis that ET-1 is involved in a salt-induced increase in glomerular pressure and suggest that ADM may act as a counterregulatory factor in this situation.
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PMID:Urinary adrenomedullin is related to ET-1 and salt intake in patients with mild essential hypertension. Salt Sensitivity Group of Italian Society of Hypertension. 1128 Dec 33

High-glucose-induced activation of mesangial cell protein kinase C (PKC) contributes significantly to the pathogenesis of diabetic nephropathy. Excess glucose metabolism through the polyol pathway leads to de novo synthesis of both diacylglyerol (DAG) and phosphatidic acid, which may account for increased mesangial cell PKC-alpha, -beta, -delta, -epsilon, and -zeta activation/translocation observed within 48-h exposure to high glucose. Raised intracellular glucose causes generation of reactive oxygen species that may directly activate PKC isozymes and enhance their reactivity to vasoactive peptide signaling. In both diabetic rodent models of diabetes and cultured mesangial cells, PKC-beta appears to be the key isozyme required for the enhanced expression of transforming growth factor-beta(1), initiation of early accumulation of mesangial matrix protein, and increased microalbuminuria. Enhanced collagen IV expression by mesangial cells in response to vasoactive peptide hormone stimulation, e.g., endothelin-1, requires PKC-beta, -delta, -epsilon and -zeta. Loss of mesangial cell contractility to potent vasoactive peptides and coincident F-actin disassembly are due to high-glucose-activation of PKC-zeta. Inhibition of mesangial cell PKC isozyme activation in high glucose may prove to be the next important treatment for diabetic nephropathy.
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PMID:Mesangial cell protein kinase C isozyme activation in the diabetic milieu. 1199 13


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