Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dahl salt-sensitive (S) rats fed a high salt diet develop hypertension, hyperlipidemia, and progressive renal disease. Previous studies have suggested that lipids may be important in the pathogenesis of glomerulosclerosis in Dahl S rats. To investigate this possibility, Dahl S rats fed 4% NaCl chow were treated chronically with the cholesterol synthesis inhibitor lovastatin. After 22 weeks, lovastatin-treated rats had a 38% reduction in serum cholesterol, a 76% reduction in urine albumin excretion, and one-sixth the incidence of focal glomerulosclerosis compared with vehicle-treated control rats. Blood pressure in lovastatin-treated rats was significantly (p < 0.05) lower than that in vehicle-treated rats both early in the study (4 weeks of treatment) and at the end of the protocol. Lovastatin had no effect on glomerular filtration rate or glomerular ultrafiltration dynamics. The efficacy of angiotensin converting enzyme inhibitors in attenuating proteinuria and experimental glomerular disease may be dependent on sodium intake. Thus, we also investigated the effects of long-term enalapril treatment on glomerular injury in Dahl S rats fed high salt chow. Enalapril treatment (50 or 200 mg/l drinking water) significantly lowered blood pressure in Dahl S rats, but did not significantly affect albuminuria or glomerulosclerosis. Enalapril also had no effect on glomerular hemodynamics. These results suggest that lipids may be important in the development of both glomerular disease and hypertension in Dahl S rats and that angiotensin converting enzyme inhibition may not affect the course of renal disease in a setting of high salt intake.
Hypertension 1992 Nov
PMID:Lovastatin but not enalapril reduces glomerular injury in Dahl salt-sensitive rats. 142 16

To define the interplay of glomerular hypertension and hypertrophy with mesangial extracellular matrix (ECM) deposition, we examined the effects of glomerular capillary distention and mesangial cell stretching on ECM synthesis. The volume of microdissected rat glomeruli (Vg), perfused ex vivo at increasing flows, was quantified and related to the proximal intraglomerular pressure (PIP). Glomerular compliance, expressed as the slope of the positive linear relationship between PIP and Vg was 7.68 x 10(3) microns 3/mmHg. Total Vg increment (PIP 0-150 mmHg) was 1.162 x 10(6) microns 3 or 61% (n = 13). A 16% increase in Vg was obtained over the PIP range equivalent to the pathophysiological limits of mean transcapillary pressure difference. A similar effect of renal perfusion on Vg was also noted histologically in tissue from kidneys perfused/fixed in vivo. Cultured mesangial cells undergoing cyclic stretching increased their synthesis of protein, total collagen, and key components of ECM (collagen IV, collagen I, laminin, fibronectin). Synthetic rates were stimulated by cell growth and the degree of stretching. These results suggest that capillary expansion and stretching of mesangial cells by glomerular hypertension provokes increased ECM production which is accentuated by cell growth and glomerular hypertrophy. Mesangial expansion and glomerulosclerosis might result from this interplay of mechanical and metabolic forces.
 ...
PMID:Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. 143 Feb 16

To test the effect of converting enzyme inhibition (CEI) on diabetes, with or without renal insufficiency, we studied streptozotocin-induced diabetic rats, with or without reduced renal mass, which were treated with insulin in sufficient amounts to maintain glucose values in the mild to moderately hyperglycemic range. We found that diabetes increased glomerular filtration rate (GFR) (inulin clearance, 2.3 +/- 0.5 ml/min vs 1.9 +/- 0.1 ml/min; p < 0.05) and blood pressure (137 +/- 15 mm Hg vs 116 +/- 6 mm Hg; p < 0.05) but did not increase plasma atrial natriuretic peptide (ANP) values, when compared with control rats (72 +/- 38 vs 68 +/- 24 pg/ml). CEI decreased GFR and blood pressure to control values. In rats with diabetes and concomitantly reduced renal mass, hypertension, elevated ANP values, proteinuria, and glomerulosclerosis were prominent features. CEI was associated with reduced blood pressure (172 +/- 17 mm Hg vs 138 +/- 15 mm Hg; p < 0.05), without a concomitant decrease in GFR (1.1 +/- 0.1 ml/min vs 1.1 +/- 0.1 ml/min). Further, CEI reduced the elevated ANP values (140 +/- 34 pg/ml vs 66 +/- 19 pg/ml; p < 0.05) to those of control rats. CEI reduced proteinuria by 50% and ameliorated the histopathologic changes. In separate experiments, rats with 5/6th nephrectomy and hypertension but without diabetes were also found to have elevated ANP levels that decreased to control values with CEI. The data speak for a renal protective effect of angiotensin I-converting enzyme inhibition in this model but do not support a specific role for ANP in the model of diabetes with concomitantly reduced renal mass.
 ...
PMID:Effects of angiotensin-converting enzyme inhibition in diabetic rats with reduced renal function. 145 98

Clinical diabetic nephropathy in man is the consequence of the development of a specific constellation of glomerular, tubular, vascular, and interstitial structural abnormalities accompanied by highly characteristic immunohistochemical alterations that, together, are unique to diabetes. Because changes resembling the specific pathology of diabetes do not develop in patients with conditions that lead to long-standing glomerular hyperfunction (such as unilateral nephrectomy), it is unlikely that glomerular hemodynamic abnormalities per se can be the cause of diabetic nephropathy. Whether hemodynamic abnormalities represent a risk factor that, in the presence of the diabetic state, can accelerate the rate of development of the basic lesions of diabetic nephropathy is currently unclear. However, there is considerable evidence that when the renal lesions of diabetes are far advanced, factors such as systemic hypertension can determine the rate of renal functional deterioration in diabetes as in other disorders. Although the diabetic rat may be a useful model for the study of aspects of the pathogenesis of diabetic nephropathy, much confusion has resulted from the inclusion of focal segmental glomerular sclerosis as a diabetic lesion. Similarly, the acceptance of all increases in urinary protein excretions in this model as resulting from or reflecting of diabetic nephropathology can be misleading. It is concluded that treatment aimed at manipulating renal hemodynamics in diabetic patients without evidence of renal disease should remain in the realm of clinical research.
 ...
PMID:An overview of renal pathology in insulin-dependent diabetes mellitus in relationship to altered glomerular hemodynamics. 146 81

On the basis of 1263 observations a relative incidence and clinical manifestations of main morphological forms of primary glomerulonephritis (PGN) are studied. Alterations in the clinical and morphological structure of primary glomerulonephritis are noted with nephrotic forms becoming more frequent and mesangiocapillary glomerulonephritis among patients with nephrotic and nephrotic-hypertension syndrome becoming somewhat less frequent. A bimodal pattern of distribution of patients with membranous nephropathy depending on the age at the beginning of the disease indicating possibly the change of etiological factors in the age groups was established. Minimal alterations, focal-segmentary glomerulosclerosis, membranous nephropathy manifested most frequently by nephrotic syndrome or subnephrotic proteinuria. Mesangioproliferative and mesangiomembranous glomerulonephritis manifested by nephrotic, proteinuric-hematuric syndrome and were the main cause of the PGN hematuric form. The highest incidence of pronounced tubulointerstitial changes in mesangiocapillary and diffuse fibroplastic glomerulonephritis is noted this explaining a considerable lowering of the kidney function in these two forms of PGN.
 ...
PMID:[Characteristics of primary glomerulonephritis (on the basis of kidney biopsies of the Pathology Department, I. M. Sechenov Moscow Medical Academy, from 1980 to 1989)]. 147 30

Kidney biopsies of 425 patients with IgA glomerulonephritis were studied to reveal the incidence, composition and possible clinical significance of extraglomerular vascular immune deposits. IgA deposits were detected in 20 cases, IgM in 28 (in 5 together with IgA), C3 in 317 and no vascular deposits in 60 cases. C3 and IgA deposits were granular, resembling mesangial deposits, while IgM deposits were lumpy, similar to IgM deposits in sclerotic and hyalinized glomeruli. The incidence of vascular lesions in patients with IgA (30%) and C3 deposits (24%) was not significantly higher as compared to those without vascular deposits (20%), but was significantly higher in patients with IgM deposits (68%, P < 0.00004). Only the presence of vascular IgM deposits correlated significantly with severe glomerulosclerosis, arterial hypertension and elevated serum creatinine levels (all P < 0.001). We conclude that neither C3 nor IgA deposits, in spite of their suggested immune complex nature, contribute significantly to the development of vascular lesions. Lumpy IgM deposits, probably the result of insudation of plasma proteins into the blood vessel walls, were associated with advanced vascular lesions and glomerulosclerosis and are probably a part of non-immune mediated progression of IgA glomerulonephritis.
 ...
PMID:Renal extraglomerular vascular immune deposits in IgA glomerulonephritis. 147 78

Analysis and comparisons were made between the clinical and pathological data obtained from 42 cases of type I and 17 cases of type III membranoproliferative glomerulonephritis (MPGN). It was shown that type I MPGN differed from type III remarkably in following respects: (1) Nephrosis was a salient feature of type III while hypertension, impairment of renal function and hematuria were more common in type I. (2) Pathological glomerular sclerosis, tubular interstitial changes and crescents formation occurred frequently in type I but not in type III. (3) Long term prognosis for type III was much better than type I. It is concluded the type III MPGN is a distinct clinical entity which differs from the classical type I MPGN in many aspects.
 ...
PMID:[Clinical and pathological features of type I and III membranoproliferative glomerulonephritis]. 147 29

A 64-yr-old man presented with diabetes mellitus, proteinuria, hypertension and moderate renal dysfunction. Renal biopsy revealed diabetic glomerulosclerosis (diffuse lesion), IgA nephropathy and membranous nephropathy (stage 2). Both mesangial IgA and subepithelial IgG deposits were demonstrated by immunofluorescence and immunoelectron microscopy. Electron microscopic studies by immunogold method showed localization of IgA (diameter 15nm gold particles) within mesangial dense deposits and IgG (diameter 15nm gold particles) within subepithelial dense deposits. Overlapping IgA and membranous nephropathy was revealed in the same diabetic glomeruli with functional and biochemical alternations.
 ...
PMID:[A case of superimposed renal lesions of IgA and membranous nephropathy with diabetic nephropathy]. 148 12

In Wistar male rats, hypertension was induced by 5/6 nephrectomy (5/6N). Body weight, blood pressure measurements, morphological and biochemical changes were followed (at four weekly intervals) for 12 weeks after 5/6N. Renal function was assessed by daily total urinary protein (TUP), plasma creatinine concentration [(Cr)p] and creatinine clearance rate. Plasma renin concentration (PRC), aldosterone concentration and erythrocyte content of sodium [Na]E and potassium [K]E were also investigated. Significant increases in systolic blood pressure (SBP), TUP, [(Cr)p] and [Na]E occurred after 4, 8, and 12 weeks of 5/6N. Progressive glomerulosclerosis (GSC), tubular atrophy and interstitial fibrosis were observed. Positive correlations were found between GSC and SBP and TUP. Positive correlations were also found between SBP and [Na]E and [(Cr)P]. PRC was not increased and showed no correlation with SBP. It is concluded that 5/6N produced hypertension associated with a series of morphological and biochemical alterations in kidney structure and function. In this model, mechanisms other than the renin-angiotensin system may be involved.
 ...
PMID:Remnant kidney pathology after five-sixth nephrectomy in rat. I. A biochemical and morphological study. 149 78

Recent studies suggest that proteolytic enzymes located within the glomerulus are involved in the degradation of extracellular matrix components. In the present investigation glomerular proteinase activities were followed in a variety of non-immune-mediated renal diseases as well as during different dietary manipulations. Azocaseinolysis was significantly reduced in the obese Zucker rat compared with lean littermates (pH 5.4:8.9 +/- 0.4 vs 11.4 +/- 0.7; pH 7.4:5.8 +/- 0.7 vs 9.3 +/- 0.6 arb. U/mg protein). When the glomerular proteolytic capacity was measured in old rats, again a significant decline in proteolysis was observed (pH 5.4:9.8 +/- 0.8 vs 17.7 +/- 0.8; pH 7.4:6.4 +/- 0.7 vs 11.7 +/- 0.5 arb. U/mg protein). In Goldblatt hypertensive rats the unclipped kidney, which is exposed to high blood pressure, revealed lower glomerular azocaseinolytic activity compared with the contralateral clipped kidney (pH 5.4:8.1 +/- 0.4 vs 12.9 +/- 0.5 arb. U/mg protein). In parallel, the cathepsin B content was also diminished in glomeruli from kidneys exposed to hypertension. When proteinases were followed in glomeruli from intact kidneys of rats fed protein-modified diets (fraction of casein 0.05, 0.20 or 0.60) a significant fall in the activities of cysteine proteinases, e.g. cathepsin B (casein 0.05:1,498 +/- 110 vs casein 0.60:914 +/- 84 microU/micrograms DNA), as well as metalloproteinases, e.g. collagenase (casein 0.05:233 +/- 14 vs casein 0.60:137 +/- 11 microU/micrograms DNA), occurred. These data indicate that in both early and late stages of glomerulosclerosis, proteolytic activities within the glomerulus tend to be reduced, which could allow extracellular matrix accumulation. Moreover, changes in dietary protein intake resulted in profound alterations of glomerular proteinases.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of glomerular proteinases in the evolution of glomerulosclerosis. 149 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>