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)

The aim of the study was to evaluate the efficacy of enalapril and atenolol in decreasing the severity of proteinuria in hypertensive patients suffering from insulin-dependent diabetes mellitus. We studied 20 hypertensive patients. All patients had proteinuria (> 3 g/24 h) and were receiving insulin treatment. Proteinuria was measured monthly in the run-in period (3 months) and during the active drug treatment (8 months). Glomerular filtration rate, effective renal plasma flow, filtration fraction, and total renal resistance were determined after the run-in and treatment periods. The patients were randomly assigned to treatment with enalapril 20 mg/day or atenolol 100 mg/day for 8 months. In both groups blood pressure decreased significantly. After 8 months' treatment, severity of proteinuria significantly decreased both in the enalapril-treated group and in the group receiving atenolol. Glomerular filtration rate and effective renal plasma flow significantly increased, while total renal resistance decreased in the patients given enalapril, whereas glomerular filtration rate, renal plasma flow, and total renal resistance significantly decreased in the patients given atenolol. The results of this study show that enalapril and atenolol reduce proteinuria in hypertensive diabetic patients by a mechanism related to their antihypertensive effects; furthermore, the beneficial effects of enalapril might be also linked to intrarenal effects.
J Cardiovasc Pharmacol 1993 Aug
PMID:Effects of atenolol and enalapril on kidney function in hypertensive diabetic patients. 769 59

The effects of long-term oral administration of losartan on the occurrence of stroke and on mortality were investigated in young salt-loaded stroke-prone spontaneously hypertensive rats (SHR-SPs) during the treatment period (5-20 weeks of age) and up to 8 weeks thereafter. Two doses of losartan, 1 and 10 mg/kg/day, were investigated, which afforded no and only moderate antihypertensive effects, respectively. During the treatment period, losartan at both doses completely suppressed stroke and mortality and strongly opposed (low dose) or abolished (high dose) the increases in saline intake, diuresis, and proteinuria observed in controls. It markedly limited (low dose) or abolished (high dose) vascular fibrinoid necrosis formation in the brain, kidneys, and heart. Finally, losartan, especially at the high dose, reduced arterial thickening and glomerular and tubulo-interstitial lesions in the kidneys, as well as arterial thickening, infarction, and fibrosis in the heart. Eight weeks after treatment discontinuation, all animals but one (low dose) were still alive. Vascular fibrinoid necrosis development remained strongly prevented (low dose) or fully suppressed (high dose) in all investigated organs. Finally, cardiac and renal lesions tended to worsen, and proteinuria was noted only in the low-dose group. We conclude that in SHR-SPs, angiotensin II, through AT1 receptor stimulation, most likely plays a major role in fibrinoid necrosis formation, vascular proliferative changes, and stroke occurrence and that losartan, most likely independently of its effect on blood pressure, affords a full and long-lasting protection against stroke and mortality both during and after the treatment period.
J Cardiovasc Pharmacol 1993 Aug
PMID:Losartan's protective effects in stroke-prone spontaneously hypertensive rats persist durably after treatment withdrawal. 769 74

A female patient who had open heart surgery for cor triatriatum under hemodialysis, subsequent kidney transplantation and pregnancy is reported. We performed hemodialysis on the patient before, during and after heart surgery to control renal failure. Two years after heart surgery, she received a kidney graft from her mother. The kidney graft showed good function. She was treated with azathioprine and prednisone. Three years after renal transplantation she delivered a healthy male infant by elective Caesarean section at 37 weeks' gestation. Mother and infant did well following delivery. There was lack of hypertension, proteinuria, signs of graft rejection, and recurrence of heart failure during pregnancy. She showed serum creatinine level < 2 mg/dl, a prednisone of < 2 mg/kg/day. Elective Caesarean section has improved hydronephrosis due to the compression of the fetus. The aforementioned good criteria contributed to the successful pregnancy of the renal transplant patient in our experience. We believe early surgical intervention overcomes complicated heart disease even with endstage renal disease, and it gives a chance to receive renal transplantation and have a healthy child. To our knowledge, this is the first report that has described the successful management of open heart surgery under hemodialysis, subsequent renal transplantation and pregnancy in a female patient with chronic renal failure.
J Cardiovasc Surg (Torino) 1993 Feb
PMID:A case of cor triatriatum with end-stage renal disease: successful management of open heart surgery under hemodialysis, subsequent renal transplantation and pregnancy. 848 11

To investigate the role of the renin-angiotensin system (RAS) on nephrosclerosis in salt-loaded, partially nephrectomized spontaneously hypertensive rats (SHR), we evaluated the effects of angiotensin II (ANGII) blockade on the progression of nephrosclerosis with an angiotensin type 1 receptor (AT1rec) antagonist [TCV-116 (TCV)] and an angiotensin-converting enzyme (ACE) inhibitor (enalapril) at the doses equivalent in reducing systemic blood pressure (BP). SHR were five/sixths nephrectomized and were fed a high-salt diet. In addition to being significantly preventive against an increase in systolic BP, both TCV and enalapril significantly attenuated the increases in proteinuria and the renal histopathological alterations. Transcription of AT1rec mRNA in the remnant kidney was enhanced with the progression of nephrosclerosis, but was inhibited by TCV as well as enalapril. In these aspects, there were no apparent differences between effects of TCV and enalapril. The RAS system plays an important role in nephrosclerosis in partially nephrectomized SHR despite a high-salt diet, and direct ANGII blockade certainly protected the kidney against hypertensive injury in this model.
J Cardiovasc Pharmacol 1995 Oct
PMID:Renal responses to angiotensin receptor antagonist and angiotensin-converting enzyme inhibitor in partially nephrectomized spontaneously hypertensive rats. 856 16

The association between insulin resistance, obesity, and hypertension is well recognised. We examined the hypothesis that hypertension in the obese Zucker rat is related to changes in vascular reactivity. Systolic blood pressure (SBP) in conscious Zucker rats was significantly greater in obese as compared with lean animals (157 +/- 9 and 117 +/- 8 mm Hg). Obese animals also had marked proteinuria and reduced urinary creatinine excretion in 24 h as compared with their lean counterparts. The reactivity of isolated aorta to phenylephrine (PE) and 5-hydroxy-tryptamine (5-HT) was modestly (twofold) increased in obese animals (EC50 13.8 nM as compared with 29.4 nM in lean animals and 0.19 nM as compared with 0.46 nM in lean animals, respectively). In the perfused mesenteric vascular bed, basal perfusion pressure was the same in both phenotypes, as was the pressor response to PE and depressor response to acetylcholine (ACh) and sodium nitroprusside (SNP). In the isolated aorta, from obese animals, insulin attenuated the contractile response to PE but markedly enhanced the vasoconstrictor potency of 5-HT. It had no significant effect on pressor or depressor responses in the perfused mesenteric bed. The data suggest that increased reactivity of central arteries to spasmogenic agents may be involved in the development of systolic hypertension in the hyperinsulinaemic Zucker rat.
J Cardiovasc Pharmacol 1995 Nov
PMID:Effects of genetic hyperinsulinaemia on vascular reactivity, blood pressure, and renal structure in the Zucker rat. 863 85

Blockade of the renin-angiotensin system (RAS) prevents the increase in blood pressure (BP) induced by chronic administration of NG-nitro L-arginine methyl ester (L-NAME) in rats. In the present study, we showed how a converting enzyme inhibitor can prevent the end-stage tissue damage due to chronic nitric oxide (NO) synthase blockade and thus improve the survival rate. Three experiments were performed. In the first, rats (n = 10) were given L-NAME (50 mg/kg) and 10 other rats were given L-NAME plus quinapril (10 mg/kg) starting 1 month after L-NAME administration. Ten untreated rats were used as controls. Rats were killed after 2 months, and the RAS, renal function, and renal morphology were analyzed. In the second experiment, a similar protocol was used, and function and morphological damage in renal slices and cervical medullary tissue were assessed after 4 months of L-NAME and 3 months of quinapril + L-NAME. In the third experiment, a similar protocol was used, but to establish survival curves, the animals were not killed. L-NAME significantly increased BP without causing any significnat changes in plasma renin activity (PRA) at 2 months. The aortic wall cyclic GMP content was significantly decreased, and the angiotensin-converting enzyme (ACE) activity was increased by L-NAME. Quinapril significantly reversed the high BP induced by L-NAME without changing the decrease in the aortic wall cyclic GMP. Two-month L-NAME treatment decreased renal function and damaged renal tissue. Quinapril prevented both proteinuria and morphological damage. Four-month L-NAME treatment induced renal end-stage damage and infarctions of the cervical medulla. Quinapril prevented this end-stage damage in the kidney and cervical medulla. Quinapril therefore prevented the increased mortality due to L-NAME. Hence, inhibition of ACE, despite its lack of effect on arterial wall cyclic GMP, does reverse the hypertension and prevent end-stage vascular damage induced by chronic L-NAME in target organs.
J Cardiovasc Pharmacol 1996 Jul
PMID:Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition. 879 48

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.
J Cardiovasc Pharmacol 1996 May
PMID:Mibefradil, a selective calcium T-channel blocker, in stroke-prone spontaneously hypertensive rats. 885 39

We tested the hypothesis that enhanced intravascular coagulation in pregnancy could produce clinical symptoms similar to those of preeclampsia, such as hypertension, proteinuria, and edema. Having confirmed this, we then examined whether the pathological changes caused by intravascular coagulation could be suppressed by administration of antithrombin III (AT III), an endogenous inhibitor active to thrombin and factor X a. Intravascular coagulation was induced in Wistar rats on day 16-20 of pregnancy by 1-h arterial infusion of tissue thromboplastin (TP) through the left ventricle of the heart. One hour after the end of the infusion period, organ blood flows were measured by the radioactive ((57)Co-labeled) microsphere method, and fibrin deposition in organs was measured by radiolabeling with [(125)I] fibrinogen injected before TP infusion. Infusion of TP produced fibrin deposition in the kidney, lung, and liver, but not in the myometrium and placenta, as well as an 80% decrease in renal blood flow (RBF), with oliguria and proteinuria. TP also caused an increase in blood pressure (BP) accompanied by an increase in plasma renin activity (PRA), both of which were suppressed by bilateral nephrectomy before TP infusion. The prophylactic administration of AT III concentrates (60 or 300 U/kg intravenously (i.v.), followed by infusion of 30 or 150 U/kg/2 h, respectively) prevented all pathological changes in a dose-dependent manner. AT III increased placental blood flow regardless of the state of coagulation. These findings suggest that intravascular coagulation plays a significant part in the pathophysiology of preeclampsia and that AT III concentrates may have therapeutic potential in the treatment of this condition.
J Cardiovasc Pharmacol 1996 May
PMID:Antithrombin III prevents renal dysfunction and hypertension induced by enhanced intravascular coagulation in pregnant rats: pharmacological confirmation of the benefits of treatment with antithrombin III in preeclampsia. 885 41

Beraprost sodium is a stable analog of the vasodilator, platelet antiaggregatory eicosanoid, prostacyclin. Experiments were performed to determine whether long-term therapy with beraprost produces vascular protective effects in saline-drinking stroke-prone spontaneously hypertensive rats (SHRSPs). Oral beraprost at 30, 100, or 300 micrograms/kg/day starting at 8.4 weeks of age did not affect the progressive increase of systolic blood pressure (measured by tail-cuff plethysmography) in these rats. Additional experiments in SHRSPs, prepared for continuous monitoring of blood pressure by radiotelemetry, revealed that oral beraprost administration reduced mean arterial pressure but that these hypotensive responses were not sustained (< 4 h). In all SHRSPs receiving oral beraprost, proteinuria and cerebrovascular lesions developed. In contrast, continuous subcutaneous infusion of beraprost at 2.8 mg/kg/day from age 8.3-12.3 weeks reduced systolic blood pressure and markedly diminished the development of renal lesions and the occurrence of stroke in saline-drinking SHRSPs. Beraprost at 0.9 mg/kg/day reduced blood pressure less than did 2.8 mg/kg/day and provided partial protection against cerebral and renal lesions after a 4-week infusion period. These results indicate that long-term subcutaneous infusion of beraprost can protect saline-drinking SHRSPs against stroke and renal damage. This effect is not readily dissociated from the ability of beraprost to reduce blood pressure in SHRSPs.
J Cardiovasc Pharmacol 1997 Sep
PMID:Beneficial action of beraprost sodium, a prostacyclin analog, in stroke-prone rats. 930 Mar 10

To investigate the role of endothelin (ET) in severe hypertension, endothelial dysfunction hypercholesterolemic stroke-prone spontaneously hypertensive rats (SHRSP on a 5% cholesterol diet) were additionally fed with 1% NaCl and 0.023% nitro-L-arginine. Under these conditions, all untreated rats died within 30 days (median 17 days). A significant prolongation of survival (median 33 days) was achieved by combination treatment with hydralazine and the ETA receptor antagonist LU 135252. Monotherapy was less effective (LU 135252 18 days; hydralazine 28 days). Likewise, only treatment with the combination completely prevented the increase in systolic arterial pressure (SAP) seen in the control group during the first 10 days and delayed development of hypertension during the subsequent observation period. The superior efficacy of the combination was also reflected by improved kidney function. After 20 days of treatment, proteinuria had only increased to 1,272 +/- 135 mg/kg/day, a reduction of 45% compared to the untreated control group (2,300 +/- 346 mg/kg/day; p < 0.05). In this animal model of aggravated hypertension and endothelial dysfunction, the combination of LU 135252 with hydralazine was superior compared to either monotherapy. Therefore, the combination of an ETA receptor antagonist with vasodilators may be a potent therapy to improve blood pressure, renal function, and survival in severe hypertension with concomitant metabolic disease.
J Cardiovasc Pharmacol 1998
PMID:Endothelin-A receptor antagonist combined with hydralazine improves survival and renal function in hypertensive rats. 959 50


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