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)

A single i.v. injection of daunomycin (10 mg/kg) into rats produced severe proteinuria and hypercholesterolemia without atherosclerosis on the 20th and 40th days after the treatment. However, these changes were not observed on the 5th day. No change in systolic blood pressure was seen through the 40-day experimental period. Relaxation to acetylcholine, A23187 and nitroprusside was examined in aortic rings precontracted with phenylephrine (3 x 10(-6) M). Acetylcholine-induced relaxation was significantly attenuated in the nephrotic rats on the 20th and 40th days, in comparison to the control animals. In aortic rings taken from control and nephrotic rats on the 40th day, removal of the endothelium or treatment with methylene blue (10(-5) M) completely abolished the relaxation induced by acetylcholine (10(-5) M). In addition, acetylcholine (10(-5) M) induced a transient increase in the aortic cyclic GMP and this increase was completely abolished by removal of the endothelium. In the preparations of nephrotic rats on the 20th and 40th days, the cyclic GMP levels stimulated by acetylcholine (10(-5) M) were decreased to about 50% in comparison to their respective control. A23187 also evoked diminished relaxation in nephrotic rats on the 20th and 40th days. However, on the 40th day after the treatment, the effects of nitroprusside in relaxing the aorta and in elevating the cyclic GMP level in the aorta were not altered by nephrosis. In addition, the nitroprusside-induced relaxation and cyclic GMP accumulation were not affected by removal of the endothelium. These results indicate that endothelium-dependent relaxation is attenuated with the development of nephrosis.
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PMID:Impaired endothelium-dependent relaxation in isolated thoracic aorta of rats with daunomycin-induced nephrosis. 207 10

We determined the renal and depressor activities of 10, 50, and 100 pmol/kg per minute i.v. of human atrial natriuretic peptide-(99-126) in conscious one-kidney, one clip dogs with chronic hypertension and modest renal dysfunction, as indicated by mild proteinuria. Atrial natriuretic peptide increased fractional sodium excretion by 0.009 +/- 0.002, 0.042 +/- 0.005, and 0.049 +/- 0.007, respectively; urinary excretion of atrial natriuretic peptide by -0.4 +/- 0.8, 3.3 +/- 1.4, and 15.8 +/- 7.4 fmol/min; and cGMP excretion by 0.65 +/- 0.06, 1.65 +/- 0.08, and 4.88 +/- 0.85 nmol/min in one-kidney shams. The changes in fractional sodium excretion were significantly attenuated in the hypertensive dogs (0.005 +/- 0.002, 0.018 +/- 0.003, and 0.022 +/- 0.004, respectively) despite exaggerated increases in atrial natriuretic peptide excretion (3.3 +/- 1.6, 22.0 +/- 5.0, and 46.6 +/- 10.8 fmol/min) and cGMP excretion (0.96 +/- 0.47, 4.51 +/- 1.27, and 7.06 +/- 1.38 nmol/min). The slope of the line relating urinary atrial natriuretic peptide to cGMP was significantly suppressed in the hypertensive dogs, suggesting a downregulation of the guanylate cyclase-linked receptors. The slope of the relationship between cGMP excretion and the natriuretic response was also depressed in the hypertensive dogs, indicating possible impairment of cGMP signal transduction. The differences between sham and hypertensive dogs were diminished when urinary levels of atrial natriuretic peptide were maximized by prior treatment with SQ 28603, an inhibitor of neutral endopeptidase EC 3.4.24.11. Atrial natriuretic peptide caused comparable decreases in mean arterial pressure and increases in glomerular filtration rate in sham and hypertensive dogs, suggesting similar vascular reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide in chronically hypertensive dogs. 755 24

An endothelin urinary hyperexcretion, which is not counterbalanced by an adequate increase in cGMP biosynthesis, was previously detected in some patients with IgA Nephropathy (IgAN). Since this imbalance might potentiate local ET1-mediated hemodynamics effects, 9 IgAN patients with an increased (> or = 0.1) urinary ET1/cGMP ratio (group 1) and 5 IgAN patients with comparable renal function and reduced ET1/cGMP ratio (group 2) were given standard doses of isosorbide 5 mononitrate (as a nitric oxide source). Blood nitric oxide (NO) levels, as detected by electron paramagnetic resonance, significantly increased after isosorbide administration (p < 0.01) and decreased after drug discontinuation in both groups. Nitric oxide levels were significantly related with those of the effective renal plasma flow (p < 0.02), but not with the glomerular filtration rate. Proteinuria levels significantly decreased after drug administration (p < 0.009) in group 1 and returned to baseline levels thereafter, except two cases showing persisting low levels. Values of filtration fraction in the same group decreased after iso5M administration (p < 0.02 compared to basal levels). These results may possibly be related to the counterbalancing effects of nitric oxide on endothelin-mediated mesangial contraction.
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PMID:Isosorbide 5 mononitrate administration increases nitric oxide blood levels and reduces proteinuria in IgA glomerulonephritis patients with abnormal urinary endothelin/cyclic GMP ratio. 855 32

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.
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PMID:Improved survival in rats administered NG-nitro L-arginine methyl ester due to converting enzyme inhibition. 879 48

The aim of the present study was to investigate the influence of age and an increased intake of dietary sodium on the cardiovascular and renal effects of the angiotensin converting enzyme inhibitor, ramipril. Male spontaneously hypertensive rats (SHR) aged 10 and 60 weeks received either control or a high level of sodium (0.3% vs. 2.6% Na) and ramipril (2 mg/kg/day) mixed in the chow for 6 weeks. Blood pressure was measured weekly by tail-cuff method. Arterial functions were determined by measuring vascular contractile and relaxation responses of mesenteric arterial rings in vitro at the end of the study. An age-related increase in systolic blood pressure, left ventricular (LVH) and renal hypertrophy (RH) as well as proteinuria were found in SHR. The vascular relaxation to nitroprusside was impaired in aged SHR. The high sodium intake accelerated the development of hypertension only in young SHR but increased LVH and RH in both age groups. Ramipril effectively lowered blood pressure in both age groups, but decreased the LVH significantly only in young rats. Ramipril markedly improved the vascular relaxation to acetylcholine and nitroprusside only in young rats. The vascular contractile responses to noradrenaline and potassium chloride were not affected by age, sodium intake or ramipril treatment. The high sodium intake markedly attenuated the cardiovascular effects of ramipril. The high-sodium diet enhanced the urinary excretion of cyclic GMP in both age groups, while it increased urinary excretion of protein in young SHR only. In conclusion, the cardiovascular effects of ramipril were impaired with advanced age even in the presence of a control intake of sodium. A high sodium intake attenuated or even abolished the cardiovascular effects of ramipril in both young and aged SHR.
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PMID:Influence of age and dietary sodium on the cardiovascular and renal effects of ramipril in spontaneously hypertensive rats. 937 79

1. The obese fa/fa Zucker rat is a genetic model of obesity and insulin resistance which develops a number of metabolic and endocrine features of non-insulin-dependent diabetes, including hypertension, proteinuria and glomerular sclerosis. 2. We have investigated the urinary excretion of the metabolites of thromboxane (thromboxane B2) and prostacyclin (6-keto prostaglandin F1 alpha), and of endothelin and cyclic GMP as markers for changes in the balance of renal haemodynamic factors in the obese Zucker rat. 3. Obese fa/fa Zucker rats were hypertensive compared with their lean counterparts (161 +/- 3 and 138 +/- 3 mmHg respectively, P < 0.01); obese animals were also markedly proteinuric (16.7 +/- 6.7 versus 1.1 +/- 0.1 mg/ml) and albuminuric (8.3 +/- 2.9 versus 0.4 +/- 0.25 mg/ml) and excreted less creatinine than lean animals (all P < 0.01). Urinary excretion of endothelin was greater in obese rats (123 +/- 24 versus 62 +/- 10 pg/15 h, P < 0.05) as was the level of pre-proendothelin mRNA, but excretion of cyclic GMP was depressed (12.5 +/- 1.6 versus 27.2 +/- 3.1 nmol/ 15 h, P < 0.01). Histological examination of kidneys from obese animals showed evidence of focal glomerulosclerosis and cortical tubular damage. 4. These results show that increased urinary endothelin is associated with proteinuria and early stage nephropathy in this animal model of non-insulin-dependent diabetes mellitus. This finding, coupled with a decreased excretion of cyclic GMP, suggests that these increased renal vasoconstrictor/vasodilator forces might contribute to the renal functional changes in non-insulin-dependent diabetes mellitus.
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PMID:Elevated renal endothelin-I clearance and mRNA levels associated with albuminuria and nephropathy in non-insulin-dependent diabetes mellitus: studies in obese fa/fa Zucker rats. 949 94

Normal pregnancy is characterized by a significant reduction in total peripheral vascular resistance and decreased pressor responsiveness to vasodilator agents. This review will consider whether nitric oxide (NO) contributes to these changes, and whether a deficiency of NO produces a preeclampsia like syndrome. The biosynthesis of NO increases in pregnant animals, as assessed by the raised plasma concentration, urinary excretion and metabolic production rate of guanosine 3',5'-cyclic monophosphate (cGMP), the second messenger of NO. In addition, urinary excretion of nitrate, the stable metabolites of NO, increases during pregnancy, paralleling the rise in cGMP. Several studies provide convincing evidence indicating that expression and activity of different NO synthases (NOS) are increased in gravid animals. Acute blockade of NOS causes a dose response increase in blood pressure and reverses the blunted vasopressor response to vasoconstrictor agents. Long-term NOS inhibition produces a pre-eclampsia like syndrome, characterized by maternal hypertension, proteinuria, thrombocytopenia, and renal damage, and lower litter size and fetal weight. Both acute and chronic responses are reduced when L-arginine, the substrate for NOS, is administered in high doses, indicating that these changes are specific to NO inhibition. In conclusion, present data suggest that a disturbance in NO release may contribute to the pathogenesis of pre-eclampsia.
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PMID:Role of nitric oxide in maternal hemodynamics and hormonal changes in pregnant rats. 983 May 12

To date, no specific treatment is established in mesangial proliferative glomerulonephritis in humans. Specific stimulation of soluble guanylyl cyclase (sGC), an enzyme catalyzing the synthesis of cGMP from GTP, can be achieved by the novel pyrazolopyridine derivative BAY 41-2272. The effect of sGC stimulation via BAY 41-2272 on mesangial proliferation was assessed in vivo using a mesangial proliferative glomerulonephritis model in rats (anti-Thy1 model). Renal biopsies, as well as glomerular isolates, urine samples, and blood samples were compared in BAY 41-2272- and placebo-treated groups during anti-Thy1 nephritis. The sGC beta(1)-subunit is upregulated during anti-Thy1 nephritis and mainly confined to mesangial areas by immunohistochemistry. Specific therapeutic sGC stimulation during anti-Thy1 nephritis in vivo was achieved via BAY 41-2272 treatment as demonstrated by increased glomerular cGMP levels causing inhibition of mesangial proliferation, glomerular matrix accumulation, and proteinuria compared with placebo-treated animals. sGC is tightly regulated in glomeruli during experimental glomerulonephritis. Considering its beneficial antiproliferative, antifibrotic, and antiproteinuric effect in experimental glomerulonephritis, the therapeutic stimulation of sGC could become a promising future goal in mesangial proliferative glomerulonephritis in humans.
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PMID:Stimulation of soluble guanylyl cyclase inhibits mesangial cell proliferation and matrix accumulation in experimental glomerulonephritis. 1556 76

In DOCA-salt hypertension, renal kallikrein levels are increased and may play a protective role in renal injury. We investigated the effect of enhanced kallikrein levels on kidney remodeling of DOCA-salt hypertensive rats by systemic delivery of adenovirus containing human tissue kallikrein gene. Recombinant human kallikrein was detected in the urine and serum of rats after gene delivery. Kallikrein gene transfer significantly decreased DOCA- and salt-induced proteinuria, glomerular sclerosis, tubular dilatation, and luminal protein casts. Sirius red staining showed that kallikrein gene transfer reduced renal fibrosis, which was confirmed by decreased collagen I and fibronectin levels. Furthermore, kallikrein gene delivery diminished myofibroblast accumulation in the interstitium of the cortex and medulla, as well as transforming growth factor (TGF)-beta1 immunostaining in glomeruli. Western blot analysis and ELISA verified the decrease in immunoreactive TGF-beta1 levels. Kallikrein gene transfer also significantly reduced kidney weight, glomerular size, proliferating tubular epithelial cells, and macrophages/monocytes. Reduction of proliferation and hypertrophy was associated with reduced levels of the cyclin-dependent kinase inhibitor p27(Kip1), and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK). The protective effects of kallikrein were accompanied by increased urinary nitrate/nitrite and cGMP levels, and suppression of superoxide formation. These results indicate that kallikrein protects against mineralocorticoid-induced renal fibrosis glomerular hypertrophy, and renal cell proliferation via inhibition of oxidative stress, JNK/ERK activation, and p27(Kip1) and TGF-beta1 expression.
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PMID:Kallikrein gene transfer reduces renal fibrosis, hypertrophy, and proliferation in DOCA-salt hypertensive rats. 1588 73

Upregulating the heme oxygenase (HO) system removes the prooxidant heme, and thus is cytoprotective. Additionally, the products from the HO pathway including, carbon monoxide, bilirubin, and biliverdin, scavenge reactive oxygen species, inhibit lipid peroxidation, and suppress tissue inflammation, while the iron formed enhances the synthesis of the antioxidant ferritin. Deoxycorticosterone acetate (DOCA)-salt hypertension, a model of human primary aldosteronism, causes oxidative stress and impairs renal function by stimulating inflammatory/oxidative transcription factors such as NF-kappaB and activating protein (AP-1). The effect of the HO system in end-organ damage in mineralocorticoid-induced hypertension has not been fully characterized. In this study, the administration of the HO inducer hemin lowered blood pressure (191 vs. 135 mmHg; n = 22, P < 0.01), increased creatinine clearance, and reduced kidney hypertrophy proteinuria, albuminuria, and histopathological lesions, including glomerular hypertrophy, glomerulosclerosis, tubular dilation, tubular cast formation, and interstitial mononuclear cell infiltration in nephrectomy/DOCA-high-salt-hypertension. The renoprotection was accompanied by reduced levels of NF-kappaB, AP-1, fibronectin, transforming growth factor (TGF)-beta, and 8-isoprostane, a marker of oxidative stress. Correspondingly, a robust increase in total antioxidant capacity, HO activity, cGMP, and an antioxidant like ferritin was observed in hemin-treated animals. Our findings suggest that suppression of oxidative/inflammatory insults alongside the corresponding decline of fibronectin and TGF-beta, an activator of extracellular matrix proteins, may account for the attenuation of renal histopathological lesions and the antihypertrophic effects of hemin. The multifaceted interaction among the HO system, TGF-beta, fibronectin, AP-1, and NF-kappaB may be explored to design new drugs against end-stage-organ damage.
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PMID:Hemin therapy attenuates kidney injury in deoxycorticosterone acetate-salt hypertensive rats. 1911 43


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