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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with severe hypertension with retinoscopic bilateral papilloedema only are not classically regarded as having malignant hypertension (MHT). We have encountered 23 such patients between 1965-1993, whilst over a similar period we have seen 315 patients who fulfilled the conventional criteria for MHT with bilateral retinal haemorrhages, exudates with or without papilloedema. We hypothesised that patients with "lone" papilloedema and severe hypertension were suffering from a disease which was identical in aetiology and outcome to conventional MHT. There were no significant differences in age, mean blood pressure, proteinuria or renal function at presentation, ethnic composition, smoking status and followup blood pressure control between the papilloedema group and those presenting with conventional MHT. Clinical features at presentation in the papilloedema only group included strokes in 4, visual disturbance in 2, headaches in 3 and heart failure in 1 patient. Many patients however had no complications at presentation. After a mean followup of 59.8 months, of the "lone" papilloedema group, 7 patients (30.4%) were still alive, 1 patient was on renal dialysis therapy, 13 were dead (56.5%) and 2 (8.7%) were lost to followup. The commonest causes of death were stroke in 4 patients, renal failure in 4 and heart disease in 2. This was a similar pattern of mortality to those patients with "conventional" MHT. Lifetable analyses showed a median survival of 35.9 months for the papilloedema group which was significantly worse than the 108.7 months for the conventional MHT group (Lee-Desu statistic 4.04, p = 0.045). We suggest that patients with high blood pressure and lone bilateral papilloedema may comprise a hitherto unrecognised subgroup of patients with MHT. Once intracerebral pathology has been excluded, these patients need to be treated as aggressively as those with MHT.
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PMID:Severe hypertension with lone bilateral papilloedema: a variant of malignant hypertension. 874

The protective effects of ME3221, 3-methoxy-2,6-dimethyl-4-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-y l]methoxy] pyridine, on aged (32-week-old) stroke-prone spontaneously hypertensive rats (SHRSP) were studied following long-term (for 8 months) oral administration. At a dose of 10 mg/kg/day, ME3221 suppressed the mortality and the hypertensive complications observed in control SHRSP: cerebral apoplexy (hemorrhage, and spongeform and malacia in the cerebral cortex), increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity, and cardiac hypertrophy and pleural effusion. The protective activity of ME3221, a surmountable angiotensin AT1-receptor antagonist, was comparable to losartan, an insurmountable AT1-antagonist, and also to enalapril, an angiotensin-converting enzyme inhibitor. In addition, ME3221 reduced the systolic blood pressure more effectively than the two reference drugs.
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PMID:ME3221, a surmountable angiotensin AT1-receptor antagonist, prevents hypertensive complications in aged stroke-prone spontaneously hypertensive rats. 879 Nov 70

In pregnant stroke-prone spontaneously hypertensive rats, salt-loading causes symptoms similar to those of human preeclampsia, such as hypertension and proteinuria. To seek evidence of the therapeutic potential in preeclampsia of antithrombin III (AT III), which is a serine protease inhibitor active on various enzymes of the coagulation cascade, we examined the effect of consecutive treatment with AT III on hypertension and proteinuria in this animal model. Salt-loading (2% NaCl diet) caused a significant elevation of systolic blood pressure on day 15-17 and of urinary protein excretion on day 17-19 of gestation, as compared with animals fed a normal diet. AT III, administered i.v. at a dose of 60 or 300 U/kg/d for 10 d from day 9-11 to 18-20, attenuated these pathological changes in a dose-dependent manner. Histological examination of the kidney revealed that AT III prevented the occurrence of arteriosclerosis and thickening of the capillary basement membrane. However, the pathological changes induced by salt-loading were not attributable to activation of the blood coagulation system. These results demonstrate that AT III has preventive action against salt-induced hypertension and proteinuria in pregnancy through a mechanism largely independent of its anticoagulant action. AT III may thus be beneficial for the treatment of clinical symptoms of preeclampsia.
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PMID:Antithrombin III prevents blood pressure elevation and proteinuria induced by high salt intake in pregnant stroke-prone spontaneously hypertensive rats. 879 79

1. Stroke-prone spontaneously hypertensive rats (SHRSP) fed a high salt diet rapidly develop proteinuria, a marker of renal damage. We have recently shown that supplementing the diet of these rats with pure omega-3 fatty acids can inhibit the development of proteinuria. The aim of the present study was to examine the underlying renal pathology and to see whether a similar benefit could be obtained with fish oil or canola oil. 2. Diets containing sodium (2% by weight) and 5% fish oil, canola oil, olive oil or safflower oil (the latter two serving as controls) were fed to groups of eight young SHRSP and the development of hypertension and proteinuria was monitored. After 9 weeks, rats were killed and their kidneys were taken for histological examination and fatty acid analysis. Urinary protein was characterized electrophoretically. 3. Patterns of protein excretion were consistent with the appearance of pathological changes in both glomeruli and tubules. Fish oil inhibited the elevation of blood pressure, prevented the development of proteinuria and minimized histological lesions. However, in rats fed canola oil, hypertension and renal damage were equally severe as in rats fed olive or safflower oil. 4. The prevention of hypertensive renal damage by dietary fish oil may be attributable to the increased incorporation of long-chain omega-3 fatty acids in the kidney.
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PMID:Dietary fish oil prevents the development of renal damage in salt-loaded stroke-prone spontaneously hypertensive rats. 880 May 75

The histologic diagnosis of diabetic glomerulosclerosis was made in 14 renal transplant recipients. All 14 had insulin-dependent diabetes mellitus, which was the original cause of end-stage renal disease in 12; one patient had membranoproliferative glomerulonephritis and another patient had membranous nephropathy as the cause of end-stage renal disease. Insulin-dependent diabetes mellitus was diagnosed at an average age of 18.5 years (range, 8-41 years), and the mean duration of diabetes prior to transplantation was 15 years (range, 2-25 years). All patients were recipients of first kidney transplants (six living related donors and eight cadavers). The histologic diagnosis of diabetic glomerulosclerosis was made on average, 97 months after transplantation (range 41-154 months). All 14 patients had proteinuria (mean 5.3 g/24 hr; range 1.1-12 g/24 hr) and renal dysfunction (mean serum creatinine level, 2.8 mg/dl). Patient and graft survival rates at 1 year, 5 years, and 10 years after transplantation were 100%, 92%, and 59%, and 100%, 92%, and 34%, respectively. Graft failure was due to diabetic nephropathy in seven patients, diabetic nephropathy and membranous nephropathy in one patient, and death due to a cerebrovascular accident in one patient. A total of five patients are alive with a functioning kidney. Of the eight patients who returned to dialysis, four are alive, three remain on dialysis, and 1 had a combined kidney and pancreas transplant. Histologic findings were as follows: 9/14 had moderate or severe diffuse glomerular basement membrane thickening and 2/14 had nodular glomerulosclerosis. Arteriolar lesions were prominent in all cases and was graded moderate or severe in 11 cases. The development of allograft diabetic nephropathy is associated with a high rate of allograft failure.
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PMID:Diabetic nephropathy after renal transplantation. Clinical and pathologic features. 883 Aug 28

Several types of antihypertensive agents, including calcium antagonists, have been reported to prevent stroke and prolong survival in stroke-prone spontaneously hypertensive rats (SHR-SP). We investigated whether mibefradil, a new calcium antagonist acting selectively at the level of T-type calcium channels, would be able to (a) limit or prevent the structural and functional alterations that develop in the cerebral arteries of SHR-SP before stroke and (b) suppress stroke and prolong survival. Mibefradil (30 mg/kg/day) was given orally to young salt-loaded SHR-SP from age 5 weeks to age 20 weeks. Blood pressure (BP) (in conscious animals), diuresis, and proteinuria were determined weekly. After 1012 weeks of treatment, middle cerebral arteries and aortas were removed from randomly selected control and treated SHR-SP. Aortic media thickness and collagen density were evaluated by histomorphometry. Middle cerebral arteries were mounted in a myograph for wall thickness determination and isometric tension recordings. Mibefradil completely prevented stroke and mortality, significantly limited the increase in BP, and opposed the increases in diuresis and proteinuria observed in controls. Simultaneously, mibefradil abolished vascular fibrinoid necrosis formation in the brain and reduced arterial thickening in the cerebral artery as well as in the aorta. The maximal contractile responses of the cerebral arteries to potassium chloride and serotonin were greater in mibefradil-treated animals than in controls, as were the endothelium-dependent relaxant responses. Mibefradil, chronically administered to young SHRSP in a dose that limits the development of hypertension not only prevents stroke and mortality but also affords protection against the vascular structural alterations which develop with age in these animals and preserves or improves the cerebral artery's smooth muscle and endothelial cell functions.
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PMID:Mibefradil, a selective calcium T-channel blocker, in stroke-prone spontaneously hypertensive rats. 885 39

Experiments were performed to determine the effect of chronic therapy with the potent and long-acting thromboxane (TX) A2/prostaglandin endoperoxide (TP) receptor antagonist, ifetroban, on hypertension development and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP instrumented with radiotelemetry probes, for continuous monitoring of arterial blood pressure, were given 1% NaCl to drink and Stroke-Prone Rodent Diet and were chronically treated with ifetroban (20 mg/kg/day, n = 10) or vehicle (n = 12) starting at 16.5 weeks of age. Ifetroban did not affect blood pressure or the development of proteinuria and cerebrovascular lesions. Chronic administration of a higher dose ifetroban (40 mg/kg/day) starting at 7 weeks of age was also without effect on blood pressure and stroke in noninstrumented saline-drinking SHRSP. These results do not support a major role for TXA2 and its endoperoxide precursors in the elevation of blood pressure and the development of cerebrovascular lesions in saline-drinking SHRSP.
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PMID:Effect of ifetroban, a thromboxane A2 receptor antagonist, in stroke-prone spontaneously hypertensive rats. 886 99

1. A comparison was made on the protective effects of the following: ME3221, a competitive angiotensin AT1 receptor antagonist; losartan, in which a major active metabolite is a non-competitive angiotensin AT1 receptor antagonist; and enalapril, an angiotensin-converting enzyme inhibitor, using the salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). 2. SHRSP received orally ME3221 (3 and 10 mg/kg per day), losartan (10 mg/kg per day) and enalapril (10 mg/kg per day) from the 6th to the 20th week of age. All the control rats showed rapid elevation of systolic blood pressure (SBP), accompanied by hypertensive complications, and died by 15 weeks of age. 3. ME3221, losartan and enalapril suppressed the elevation of SBP in the salt-loaded SHRSP to a comparable degree. ME3221 and losartan increased the survival rate to > 90%, and diminished hypertensive complications such as cerebral apoplexy (stroke), renal injury (increased proteinuria, and total N-acetyl-beta-D-glucosaminidase activity) and heart failure (cardiac hypertrophy and pleural effusion). 4. Competitive (ME3221) and non-competitive (losartan) angiotensin AT1 receptor antagonists showed comparable efficacy against the complications and mortality of the salt-loaded SHRSP; both were more potent than enalapril in the protective effect.
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PMID:Protective effects of ME3221 on hypertensive complications and lifespan in salt-loaded stroke-prone spontaneously hypertensive rats. 893 13

Remarkable advances have been made with prolonged antihypertensive therapy in reversing cardiovascular morbidity and mortality. Deaths from stroke have been reduced by 70% and from coronary heart disease by 35%. In contrast, endstage renal disease resulting from hypertension continues to increase. The explanations for this seeming paradox remain unresolved even though experimental models have demonstrated that certain antihypertensive agents may have beneficial renal and intrarenal hemodynamic effects; but reversal of the intrarenal pathological lesions have not been shown to improve. This discussion summarizes recent studies from our laboratory in aged (73- and 85-week-old) spontaneously hypertensive rats (SHR) with naturally occurring end-stage renal disease and in a model of aged SHR employing nitric oxide inhibition in younger, adult (20-week-old) SHR. Our findings demonstrated that the systemic and whole renal hemodynamics, intrarenal glomerular dynamics, proteinuria, and renal pathological lesions can be prevented or reversed with angiotensin-converting enzyme inhibition therapy but not with hydrochlorothiazide (at similar levels of arterial pressure reduction). The implications and possible mechanisms involved in the development of both naturally occurring and nitric oxide-exacerbated SHR are multifactorial, involving the endothelial nitric oxide system and its interaction with angiotensin II (and possibly bradykinin) among other factors. Moreover, these pathophysiological cellular mechanisms may be shared by the aging process as well as in naturally occurring spontaneous hypertension in the rat and, perhaps, in humans with essential hypertension. Thus, antihypertensive therapy seems to be specific in its ability to prevent and even reverse the pathophysiological derangements of renal involvement in hypertension. Thus, prevention and reversal of end-stage renal disease do not seem to require greater reduction of arterial pressure than with other target-organ involvement. However, they do require specific inhibition of the arteriolar and glomerular lesions produced by the disease.
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PMID:Arthus C. Corcoran Memorial Lecture. Influence of nitric oxide and angiotensin II on renal involvement in hypertension. 903

1. The protective effect of ME3221, a surmountable AT1 antagonist, on the hypertension and its concomitant complications in aged (32 week old) stroke-prone spontaneously hypertensive rats (SHRSP) was studied following long-term (32 weeks) oral administration, and compared with those of losartan (metabolite EXP3174 is an insurmountable AT1 antagonist) and enalapril. 2. During the treatment period, ME3221, at a dose of 10 mg/kg per day steadily reduced the systolic blood pressure, and no tolerance was developed to the fall in blood pressure. The reference drugs showed similar activity, but the antihypertensive effect of ME3221 was more potent. 3. In the control group, rats began to die from 52 weeks of age and all rats had died by 64 weeks of age. In contrast, no rats treated with ME3221, losartan or enalapril died before 64 weeks of age. 4. ME3221, losartan and enalapril suppressed the hypertensive complications observed in control SHRSP, that is, cerebral apoplexy (stroke and cerebral oedema), renal injury (increased proteinuria, total N-acetyl-beta-D-glucosaminidase activity and ascites) and heart failure (cardiac hypertrophy and pleural effusion). 5. These results indicate that ME3221 has a stable anti-hypertensive effect, prevents hypertensive complications and prolongs survival in aged SHRSP equally as well as losartan and enalapril.
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PMID:Effect of chronic treatment with ME3221 on blood pressure and mortality in aged stroke-prone spontaneously hypertensive rats. 907 29


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