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)

Glomerular hemodynamics measurements in rats with experimental membranous nephropathy [passive Heymann nephritis (PHN)] have demonstrated that the appearance of proteinuria 5 days after administration of anti-Fx1A antibody is temporally related to changes in the glomerular ultrafiltration coefficient (LpA). Previous studies in other models of glomerular injury have suggested a significant role for angiotensin II (ANG II) in the glomerular hemodynamic abnormalities. To evaluate the possible role of ANG II in the LpA decrease, converting enzyme inhibitor (CEI) was administered acutely or chronically (5 days before and after induction of PHN) to rats with PHN. Acute ANG II blockade produced a fall in mean arterial pressure (MAP), single-nephron glomerular filtration rate (SNGFR), absolute proximal reabsorption (APR), single-nephron plasma flow, single-nephron blood flow, and glomerular capillary hydrostatic pressure (PG); however, no changes in LpA were detected. Chronic administration of CEI (MK421, 5 mg.kg-1.day-1) in the drinking water was associated with a fall in MAP; however, both SNGFR and APR increased. PG and the transcapillary hydrostatic pressure gradient were unchanged, and LpA remained depressed. These results suggest that reduction of LpA in rats with PHN is ANG II independent and that other mechanisms are required to explain these changes in glomerular hemodynamics.
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PMID:Role of angiotensin II in experimental membranous nephropathy. 283 20

To provide information on the possible influence that hypertension or its treatment might have on the development of cysts in autosomal dominant polycystic kidney disease, we studied the effects of the sodium content of the diet, DOCA-salt hypertension, renovascular hypertension, and the administration of enalapril or furosemide on the development of 2-amino-4-5-diphenylthiazole (DPT)-induced renal cystic disease. DOCA-salt hypertension caused vascular and glomerular lesions and proteinuria, but it did not enhance the development of cysts. Cytogenesis was enhanced in experimental conditions where the renin-angiotensin system is known to be activated. On the other hand, interventions known to suppress the renin-angiotensin system lessened the development of cysts. We hypothesize that this effect might be mediated by intrarenal angiotensin II and its capacity to promote cell growth and to control the postglomerular vascular resistances and the compliance of the renal interstitium.
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PMID:Mechanisms affecting the development of renal cystic disease induced by diphenylthiazole. 284 32

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

Development of hypertension in Type I diabetics parallels evolution of nephropathy. In Type II diabetics, excessive prevalence of hypertension prior to the appearance of proteinuria suggests that factors other than nephropathy are operative in its pathogenesis. On the other hand, the risk of nephropathy in Type II diabetics is higher than previously appreciated. Recent evidence suggests that angiotensin II plays an important role in the induction and progression of diabetic nephropathy. This provides a rationale for antihypertensive therapy with converting enzyme inhibitors in nephropathic diabetics in whom they have been shown to lower blood pressure and diminish proteinuria. Furthermore, in a retrospective study of patients with various renal diseases (including diabetic nephropathy), the authors found suggestive evidence that converting enzyme inhibitors may also attenuate progression of renal failure to a greater extent than other antihypertensive drugs.
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PMID:Rational drug treatment of the hypertensive diabetic with nephropathy. 297 60

The purpose of this study was to define the effect of the angiotensin-converting enzyme inhibitor, enalapril maleate, on blood pressure, renal function, protein excretion, and potassium homeostasis in patients with hypertension associated with moderate to severe renal dysfunction. Nine patients, having an initial inulin clearance between 9 and 48 mL/min/1.73 m2, were treated with enalapril monotherapy (n = 6) or enalapril/furosemide (n = 3) combination therapy. Systolic and diastolic blood pressures were well controlled. Supine plasma renin activity was stimulated; the supine plasma aldosterone level was suppressed, with a resultant increase in the serum potassium level. Clinical hyperkalemia was not observed. Glomerular filtration rate, assessed by inulin and creatinine clearances, was not significantly changed. Effective renal plasma flow, assessed by paraaminohippurate clearance was significantly increased, with a resultant decrease in filtration fraction. Importantly, urinary protein excretion was markedly reduced. These results suggest that enalapril therapy produces efferent arteriolar dilitation with preservation of the glomerular filtration rate. Enalapril therapy may also blunt the effects of angiotensin II on transglomerular passage of protein, as demonstrated by reduced proteinuria. These findings suggest that interruption of the renin-angiotensin system in patients with preexisting renal disease may have renal protective effects.
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PMID:Effect of enalapril in subjects with hypertension associated with moderate to severe renal dysfunction. 302 60

An examination of the principal physiological actions of angiotensin II should make it clear why in vivo attempts to inhibit the rate of angiotensin II generation have been an attractive avenue in pursuing control of high blood pressure. The major physiological effect of angiotensin II relates to its direct pressor effect, but there are supplementary blood pressure regulating actions. Therefore, if we limit the rate of angiotensin II generation by inhibiting the angiotensin converting enzyme (ACE) we should expect to control high blood pressure in a number of clinical syndromes. This paper reviews the future of ACE inhibitors in the treatment of conditions such as hypertension associated with unilateral renal artery stenosis, essential hypertension and severe and previously unresponsive hypertension, with respect not only to efficacy but also to the side-effect profile and ancillary properties. Side effects seen with this class of drug are cough, rashes (both morbilliform and urticarial) and, rarely, angio-oedema. Proteinuria, nephrotic syndrome, leukopenia and taste disturbance were previously reported with captopril but only taste disturbance, and that less frequently, is apparent at the lower doses now employed. Several studies have examined the 'quality-of-life' aspects of ACE therapy and have usually but not always reported favourably. There are features of the ACE inhibitors which make them attractive drugs, and while we should be cautious because of limited experience, we should critically and creatively examine their properties over the next years.
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PMID:Angiotensin converting enzyme inhibition in hypertension. 331 25

Food intake increases glomerular filtration and proteinuria in adult rats. That this postprandial hyperfiltration could be age dependent was investigated in 3-, 10-, 20-, and 30-mo-old rats. Glomerular filtration rate and protein excretion were measured in fed or 24 h fasted conscious animals. In the 3-mo-old rats food ingestion increased renal filtration by 45% from 1.17 +/- 0.08 to 1.73 +/- 0.11 ml.min-1.g kidney wt-1 (n = 6). As the animals became older, the differences between fed and fasted periods became smaller: in 30-mo-old rats glomerular filtration rate was 0.85 +/- 0.03 and 1.01 +/- 0.06 ml.min-1.g kidney wt-1 (n = 6) in fasted and fed conditions, respectively. Proteinuria, which was mainly albuminuria, increased slightly with age and was more markedly reduced by acute food restriction in the 30-mo-old than in the 3-mo-old rats. Because the renin-angiotensin system activity decreases with age, its role in postprandial hyperfiltration was assessed by measuring glomerular filtration in 3-mo-old animals whose angiotensin II converting-enzyme activity was chronically inhibited by daily administration of perindopril. In such experimental conditions there was no longer a difference in renal filtration between fed and fasted rats. These data indicate that 1) postprandial increase in glomerular filtration is to some extent related to the renin-angiotensin system activity; 2) short-term reduction of food intake reduces proteinuria even in senescent rats, although the feeding dependence of the glomerular filtration is blunted with age.
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PMID:Effect of feeding on glomerular filtration rate and proteinuria in conscious aging rats. 340 83

We investigated the effect of captopril, an orally active angiotensin converting enzyme inhibitor, on urinary protein excretion in puromycin aminonucleoside nephrotic rats. The administration of captopril (10 mg/100 g body weight) decreased proteinuria on days 10-14 following the administration of puromycin aminonucleoside (73.0 versus 125.0 mg, p less than 0.01), without affecting glomerular filtration rate. The beneficial effect of captopril was not abolished by the continuous intravenous infusion of angiotensin II (10 micrograms/kg/h for 9 days) or subcutaneous injections of aprotinin (50,000 KIU/day for 3 days). Indomethacin, in moderate (5 mg/kg/day for 3 days) or high (10 mg/kg/day) doses, abolished the captopril attenuation in urinary protein excretion. The salutory effect of captopril was characterized by a reduction in the fractional excretion of protein without compromising the glomerular filtration rate. No difference in renal ultrastructure was noted in captopril-treated versus control animals. Captopril was ineffective in reducing urinary protein excretion in rats with adriamycin-induced glomerulopathy. We conclude that captopril acts to reduce proteinuria in renal disease states arising from depletion of the glomerular basement membrane polyanion. The mechanism of action is postulated to be an alteration in renal hemodynamics, namely increased blood flow and a decrease in the ultrafiltration coefficient, that are the consequence of increased intrarenal prostaglandin production.
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PMID:The effect of captopril on urinary protein excretion in puromycin aminonucleoside nephrosis in rats. 389 1

Hypertension accompanying diabetes mellitus may involve abnormalities in at least two major blood pressure-regulating systems: the body sodium-fluid volume state and cardiovascular reactivity. In metabolically stable nonazotemic diabetes, exchangeable sodium is increased by 10% on average, regardless of age, insulin dependence or nondependence, or the presence or absence of diabetic retinopathy or clinical nephropathy (proteinuria greater than or equal to 0.3 g/24 hr). Possible contributing mechanisms include renal sodium retention and an extravascular shift of fluid and sodium; intracellular accumulation is not excluded. Circulatory volume is normal or low and the total exchangeable sodium/blood volume ratio increased. In hypertensive diabetes, the latter abnormality is particularly pronounced; systolic pressure tended to correlate with exchangeable sodium (r = 0.47, p less than 0.001) and diastolic pressure with the plasma sodium/potassium ratio (r = 0.25, p less than 0.05). Plasma aldosterone, renin, epinephrine, and norepinephrine levels are generally normal or sometimes low in metabolically stable nonazotemic diabetic patients with normal or high blood pressure; the plasma clearance of norepinephrine also appears to be unaltered. The cardiovascular pressor responsiveness to norepinephrine is often exaggerated relative to concomitant plasma concentrations, regardless of age, type of antidiabetic treatment, or presence or absence of diabetic retinopathy, peripheral neuropathy, or high blood pressure. Pressor responsiveness to angiotensin II also may sometimes be increased relative to plasma renin levels. Sodium retention and diabetic vasculopathy of resistance vessels could be important complementary mechanisms of hyperreactivity. In diabetes with mild hypertension, diuretic treatment restored exchangeable sodium, norepinephrine pressor responsiveness, and blood pressure toward normal. Thus sodium retention and cardiovascular hyperreactivity tend to occur even at the normotensive, nonazotemic stage of diabetes and may concomitantly predispose for the frequent development of hypertension in the diabetic population.
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PMID:Pressor factors and responsiveness in hypertension accompanying diabetes mellitus. 390 20

The aim of the present study was to evaluate changes in urinary micro-albumin and in serum and urinary beta 2-microglobulin during treatment with captopril at low doses in a group of hypertensive outpatients without any sign of renal impairment. Thirty-four patients with essential hypertension entered the study, all having been treated for at least one year with beta-blockers and diuretics. None had proteinuria (by Albustix) and creatinine clearance was normal. The patients were randomly allocated to two groups: the first group was maintained on the previous regimen (group BD) and the second received captopril 50 mg twice daily instead of the beta-blocker (group CD). During the year of observation blood pressure values and serum and urinary beta 2-microglobulin were not significantly different between the two groups. There was, however, a significant reduction in albumin excretion rate (AER) in the CD group at both 3 and 6 months. Since arterial measures did not differ between the two groups, it is proposed that the reduction of AER was due to a diminution of the transcapillary hydraulic pressure due to the inhibition of the intrarenal angiotensin II induced by captopril.
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PMID:Long-term captopril therapy at low doses reduces albumin excretion in patients with essential hypertension and no sign of renal impairment. 391 Jul 71


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