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)

Endothelin (ET), a peptide recently isolated from the supernatant of cultured endothelial cells, is the most potent vasoconstrictive and hypertensive agent known up till now. We have examined the effect of ET-1 intravenous injection on regional hemodynamics in conscious unrestrained rats. Normal rats are instrumented with an arterial catheter for measurement of mean arterial pressure (MAP) and with pulsed Doppler flow probes on renal and mesenteric arteries and the abdominal aorta for simultaneous recording of blood flow velocities (V). These parameters allow calculation of vascular resistance (R) (R = MAP/V). Thus, ET-1 induces an initial and sharp hypotension, concomitant with tachycardia and a marked vasoconstriction of renal and mesenteric arteries, but a vasodilatation of aorta. This response is followed by a dose-dependent and long-lasting increase of MAP and of renal, mesenteric and aortic vascular resistances accompanied by a decrease of heart rate. The greatest impact of ET-1 constrictive effects is seen on the renal vascular bed whereas the abdominal aorta appears to be far less sensitive. In fact, the dose of 2 nmol/kg of ET-1 induces a dramatic and long-lasting fall of renal blood flow (-86%) resulting from an important vasoconstriction (+1818%). Finally, an elevation of proteinuria is revealed in ET-1 (2 nmol/kg) treated rats, but not in those treated with the same dose of Angiotensin II. This proteinuria is characterized by the appearance of proteins with a molecular weight from 20,000 to 140,000 and sometimes 280,000, and an increase of excreted albumin, seeming to reflect an alteration of glomerular permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The impact of endothelin on renal hemodynamics in conscious rats]. 214 78

Glomerular capillary hemodynamics influence glomerular permselectivity to macromolecules, and alterations in these factors can evoke proteinuria. Changes in hemodynamic patterns can alter protein flux by changing its diffusion- or concentration-driven movement in the presence of a constant membrane barrier. Alternatively, hemodynamic forces may disrupt, transiently or irreversibly, the permeability characteristics of the capillary barrier. Maneuvers that lower glomerular capillary pressure appear capable of reversing at least in part, these latter permeability defects. Angiotensin II, provoked by higher levels of dietary protein intake, may be a particularly important mediator of proteinuria both through its effects on diffusion-mediated protein leakage and its tendency to provoke permeability defects due to heightening of glomerular capillary hydraulic pressures.
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PMID:Hemodynamic effects of glomerular permselectivity. 225 73

In vitro release of renin, angiotensinogen and aldosterone was studied in control (CT) and nephrotic rats. Nephrotic syndrome (NS) was induced by a single injection of puromycin aminonucleoside (PA). The in vitro systems used were: renal cortical slices (RCS), liver slices (LS) and adrenal glands, all incubated in Krebs-Ringer buffer. Renal renin content (RRC) and isoproterenol-induced renin secretion (RS) also were studied. RS, RRC and angiotensinogen release were measured indirectly by radioimmunoassay (RIA) of angiotensin I (ANG I); aldosterone was estimated by direct RIA. Basal RS was not modified in NS: 385 +/- 196 (CT) vs 344 +/- 149 ng ANG I/mg protein/h (NS), p greater than 0.05. Isoproterenol increased RS significantly in both CT and NS groups: 535 +/- (CT) and 685 +/- 231 ng ANG I/mg protein/h (NS) (p less than 0.05 vs. basal RS). RRC was similar in both groups: 2.17 +/- 0.62 (CT) vs 2.05 +/- 0.49 micrograms ANG I/mg protein/h (NS), p greater than 0.05. Angiotensinogen release from LS increased in nephrotic rats from 10 +/- 3.2 (CT) to 12 +/- 1.9 pmoles angiotensinogen I/mg tissue/2h (NS), p less than 0.05. Aldosterone release increased markedly from adrenal glands of rats with NS (1649 +/- 1111 pg aldosterone/mg tissue/h) with respect to control rats (257 +/- 85), p less than 0.05 In vitro studies were performed six days after PA-injection, when nephrotic rats had ascitis, edema, proteinuria, hypoproteinemia, hypercholesterolemia, hypertriglyceridemia, low sodium and aldosterone excretion, low levels of plasma angiotensinogen and high levels of plasma renin and aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiology of experimental nephrotic syndrome induced by puromycin aminonucleoside in rats. II. In vitro release of renin, angiotensinogen and aldosterone. 226 44

Angiotensin II (ANG II) infusion has been reported to impair barrier size selectivity and exacerbate proteinuria in the rat. To examine whether this is also true of humans, we infused a pressor dose of ANG II into seven healthy controls and seven nephrotic patients. A prompt depression of glomerular filtration rate (GFR) and renal plasma flow was observed in each group (P less than 0.01). Surprisingly, the excretion rates of albumin (5.3 +/- 1.6 to 2.8 +/- 0.3 in controls and 4,791 +/- 1,244 to 3,833 +/- 800 micrograms/min in nephrotics) and immunoglobulin G (1.5 +/- 0.4 to 0.8 +/- 0.2 and 305 +/- 87 to 255 +/- 94 micrograms/min, respectively) fell significantly during ANG II infusion. Fractional clearances of dextrans of broad size distribution (radii 34-54 A) were uniformly elevated by ANG II infusion in controls but tended to decline in nephrotics. A heteroporous model of the glomerular capillary wall revealed ANG II to have a negligible effect on membrane-pore structure. However, the depressed GFR lowered the rate at which macromolecule-rich filtrate was formed through a subset of nondiscriminatory pores from 272 to 176 microliters/min in controls and from 394 to 334 microliters/min in nephrotics. We conclude that, in striking contrast to the rat, pressor ANG II infusion has little or no influence on barrier size selectivity in humans but exerts an antiproteinuric effect by lowering the filtered protein load.
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PMID:Effect of angiotensin II infusion on the human glomerular filtration barrier. 247 34

Plasma renin activity (PRA) may be high among teenage and young adult insulin-dependent diabetic subjects. Supine PRA and stimulated PRA were therefore measured in 50 female and 50 male diabetic subjects, 13-20 years old, diagnosed before the age of 16. Fifty percent have been restudied after 4.6 +/- 0.2 (mean +/- SEM) years. Initially, 43% had high PRA (supine 4.0 +/- 0.37, stimulated 12.02 +/- 0.8 ng/ml/hr angiotensin I), 45% had normal activity (supine 2.89 +/- 0.26, stimulated 6.47 +/- 0.34 ng/ml/hr/angiotensin I), and 12% had low activity (supine 1.57 +/- 0.05, stimulated 3.09 +/- 0.08 ng/ml/hr/angiotensin I). Levels were directly associated with prepubertal duration of diabetes and were inversely associated with duration of diabetes after onset of puberty but not with total duration or patient age. Within 4.6 +/- 0.2 years the percentage of subjects with high PRA fell to 13%, and the percentage of those with low PRA rose to 35%. Initially 51% of the cohort had normal albumin excretion rates (AER) at rest and during exercise equal to or less than 10 micrograms/min/m2; 32% had elevated rates only during exercise of 39 +/- 5 micrograms/min/m2; 13% had elevated rates at rest of 41 +/- 8 micrograms/min/m2 and during exercise of 116 +/- 21 micrograms/min/m2; and 4% had clinical proteinuria at rest and during each exercise period equal to or greater than 150 micrograms/min/m2. After 5 years, 58% continued to have normal AER, or their AER improved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma renin activity and albumin excretion in teenage type I diabetic subjects. A prospective study. 266 31

1. Twelve patients with the nephrotic syndrome were prescribed for 4 week periods a normal protein diet (NPD) containing 1 g of protein/kg ideal body weight. They were then prescribed for further 4 week periods in random order diets with high (HPD) and low (LPD) protein contents, respectively 2.0 and 0.5 g/kg ideal body weight. 2. Compliance was confirmed by dietary history and measurement of urinary excretion. 3. Serum albumin was the same on all diets. Twenty-four hour urinary protein excretion increased progressively with increasing dietary protein (LPD 6.1 g. NPD 8.2 g. HPD 9.2 g). Recumbent plasma renin activity and serum phosphate were significantly increased on HPD (plasma renin activity: LPD 5.7, NPD 4.6, HPD 8.2 pmol of angiotensin I min-1 1(-1); serum phosphate: LPD 1.27, NPD 1.26, HPD 1.41 mmol/l). 4. There was no evidence of protein-induced hyperfiltration or hyperperfusion: 51Cr-ethylenediaminetetra-acetate and [125I]iodohippurate clearances were similar on all three diets. 5. Since proteinuria, increased plasma renin levels and hyperphosphataemia may contribute to progression of renal failure and because HPD did not improve hypoalbuminaemia, the use of HPD in the nephrotic syndrome should be abandoned. 6. Until it can be established that LPD, which is accompanied by the least proteinuria, does not, with long-term feeding, lead to malnutrition, NPD should be used in the treatment of the nephrotic syndrome.
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PMID:Effect of a high protein diet in patients with the nephrotic syndrome. 280 3

The effects of the angiotensin converting enzyme (ACE) inhibitor enalapril on the proteinuria and degree of focal glomerular sclerosis hyalinosis (FSH) in chronic puromycin aminonucleoside nephropathy (PAN) were examined. Chronic PAN was induced in male Sprague-Dawley rats by seven subcutaneous injections of puromycin aminonucleoside (20 mg/kg) over 10 weeks (Groups I and II). Group II rats also received enalapril 10 mg/kg/day in the drinking water throughout the study (12 weeks). Group III rats served as age-matched controls. Proteinuria was similar in Groups I and II (35.5 +/- 9.7 versus 29.1 +/- 4.1 mg protein/mg creatinine, mean +/- SEM, P greater than 0.05). Serum creatinine remained unchanged in Group I, but rose from 0.7 +/- 0.04 to 1.2 +/- 0.1 mg/dl (mean +/- SEM, P less than 0.05) in Group II. FSH was 13.8% in Group I, 12.9% in Group II (P greater than 0.05), and 0.6% in Group III. There was no significant difference in glomerular lipid content and in immunofluorescence for rat albumin, fibrinogen, IgM, IgG, and C3 between Groups I and II. ACE activity was inhibited by 94% in serum, 83% in lungs, and 92% in kidneys; and blood pressure response to. Angiotensin I challenge was decreased by 50% in rats similarly treated with enalapril versus controls. In summary, proteinuria and glomerular sclerosis in this model are not affected by ACE inhibition.
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PMID:Failure of angiotensin converting enzyme inhibition to affect the course of chronic puromycin aminonucleoside nephropathy. 282 16

Angiotensin II is the main regulator of both glomerular haemodynamics and glomerular capillary permeability. An alteration in the function of intrarenal angiotensin II seems to be the cause of diabetic glomerulopathy in animals and humans. In order to investigate the renal effects of the angiotensin converting enzyme (ACE) inhibitor enalapril (5 mg once a day), 24 normotensive diabetic patients with persistent proteinuria, after a 3-month run-in period, were randomly allocated to receive the active drug (12 patients) or the corresponding placebo, for the 6 months. Effective renal plasma flow, glomerular filtration rate, renal vascular resistance and filtration fraction were measured at the end of the run-in and the treatment periods. Blood pressure, heart rate, urinary albumin excretion, plasma renin activity and aldosterone, blood glucose, serum fructosamine and body weight were checked monthly during the run-in and every 2 months during the treatment period. Enalapril decreased urinary albumin excretion in the normotensive diabetic patients without any changes in systemic blood pressure or glomerular haemodynamics. These results indicate that ACE inhibition interferes with the glomerular capillary permeability induced by angiotensin II.
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PMID:Angiotensin converting enzyme inhibition with a low dose of enalapril in normotensive diabetics with persistent proteinuria. 285 53

Captopril (Capoten; Squibb) is a specific orally active antagonist of peptidyl-dipeptide carboxyhydrolase, the enzyme which converts angiotensin I to angiotensin II and which inactivates bradykinin. Captopril therefore reduces blood pressure in a variety of animal models of hypertension. In 96 studies on 1570 patients, captopril has been shown to be superior to placebo and equivalent to either propranolol or a diuretic in the treatment of essential hypertension. In the management of severe treatment-resistant hypertension, the response to captopril (alone or in combination with a diuretic and/or propranolol) was better than the response to standard triple therapy. Captopril, with digitalis and a diuretic, also improved the haemodynamic and clinical status of patients with refractory congestive heart failure. Side-effects include skin rashes (15%), proteinuria (1,1%, or 0,4% of patients with no prior renal disease) and the nephrotic syndrome (0,9%, or 0,3% of patients with no prior renal disease). Nearly all patients with the nephrotic syndrome in whom renal biopsies were performed were found to have membranous glomerulopathy. Neutropenia (total white cell count less than 1,000/microliter) was found in 33 of over 6,000 patients (0,4%), but in all cases there were other possible causes for this. Captopril is the first of an important group of antihypertensive and afterload-reducing drugs; its major indications are likely to be in the treatment of refractory severe hypertension or congestive heart failure.
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PMID:Captopril--an overview. 621 58

Angiotensin II (Ang II) is the primary mediator of the renin-angiotensin system (RAS). Inappropriate control of the RAS is critically involved in the development and maintenance of hypertension and congestive heart failure. The actions of Ang II are thought to be mediated by specific surface receptors on the various target organs. At present, two receptors for Ang II have been firmly established in mammals, including man. According to current nomenclature, losartan represents the prototype antagonist of the Ang II type 1 (AT1) receptor and does not possess significant affinity for the so-called AT2 receptor. Losartan is the first of a new class of orally active, nonpeptide Ang II receptor antagonists able to very specifically and selectively inhibit the RAS while lacking the agonistic effects of the peptide receptor antagonists, e.g. sarlasin, or the bradykinin potentiating effects of the angiotensin converting enzyme (ACE) inhibitors. Virtually all of the known actions of Ang II, e.g. those defined by Ang II itself, saralasin, ACE or renin-inhibitors are blocked by losartan, emphasizing the major role of this distinct Ang II receptor subtype in mediating the responses of Ang II. The functional correlate of the AT2 receptor remains poorly understood. In several models of experimental and genetic hypertension, AT1 receptor antagonists are effective antihypertensive agents with similar efficacy to that of ACE and renin-inhibitors. In animal models of renal disease, AT1 receptor antagonists significantly decrease proteinuria, protect against diabetic glomerulopathy and increase survival in stroke-prone spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new class of therapeutic agents: the angiotensin II receptor antagonists. 763 3


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