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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesangial cells play an important role in physiological and pathophysiological regulation of glomerular functions. To explore the involvement of deranged mesangial cell functions in the pathogenesis of hypertension, the growth activity of mesangial cells was compared in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Upon exposure to fetal calf serum, the growth rate was significantly higher in mesangial cells cultured from glomeruli of 4-week old SHRSP than in those of age-matched WKY. This abnormally high growth of SHRSP mesangial cells was significantly inhibited by dihydropyridine calcium antagonists. Of the three antagonists tested, manidipine was the most potent inhibitor. Significant growth inhibition occurred at a concentration as low as 10(-12) M; inhibition as high as 65% was found at 10(-6) M. Calcium antagonists, particularly manidipine, may prevent or delay the development of hypertension not only through vasodilation but also through inhibition of mesangial cell growth. By slowing mesangial cell proliferation, calcium antagonists also may slow the progression of hypertension-induced glomerular sclerosis.
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PMID:Mesangial cell growth in genetically hypertensive rats and effect of calcium antagonists upon this growth. 134 84

During the past 2 decades, there have been important reductions in stroke-related morbidity and mortality due to better control of hypertension. However, there has been a lesser effect on the reduction of coronary mortality and far less of an impact on all other forms of noncardiovascular disorders such as renal disease. This suggests that our ability to prevent hypertensive nephrosclerosis through traditional methods of lowering blood pressure may not be as effective as was once thought, particularly in high-risk patients such as blacks, diabetics, the elderly, and patients with preexisting renal disease. One reason that may partially explain the difficulty in protecting the renal circulation from hypertensive damage is the interaction between antihypertensive medications and the aged-related decline in renal perfusion. Depending on their mechanism of action, antihypertensive agents may impair renal blood flow (through plasma volume contraction or reduction) and further aggravate the age-related decline in renal perfusion. A worsening of renal perfusion may activate counterregulatory neurohormonal mechanisms, such as the renin-angiotensin-aldosterone system, which in turn may place the patient at increased risk for the development of glomerulosclerosis through promotion of vascular or mesangial hypertrophic changes or increased intraglomerular pressure, despite an associated reduction in systemic blood pressure. Since antihypertensive agents have such varied effects on systemic and renal hemodynamics, an understanding of the antihypertensive actions in a given patient may have significant influence on renal function. Thus, an improved understanding about the effects of aging and hypertension on the renal microcirculation will hopefully facilitate a more physiologically appropriate antihypertensive medication selection with the expectation that renal function will be benefitted over the long term.
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PMID:Hypertensive nephropathy: is a more physiologic approach to blood pressure control an important concern for the preservation of renal function? 151 33

The relationship between hypertension and cardiovascular damage was assessed in three groups of spontaneously hypertensive rats (SHR): 1. stroke prone SHR (SHR-SP) treated orally with an angiotensin I converting enzyme inhibitor (captopril) (100-400 mg/L in the drinking water) from 6 to 35 weeks of age, 2. SHR-SP maintained on tap water until 30 weeks of age, 3. stroke resistant SHR (SHR-SR) maintained on tap water. The controls were Wister Kyoto rats (WKY) maintained on tap water. Captopril-treated SHR-SP showed blood pressure lower than that of untreated SHR-SP, similar to SHR-SR. The ratio of heart weight to body weight was 0.55% in SHR-SP, 0.39% in captopril-treated SHR-SP, 0.46% in SHR-SR, and 0.39% in WKY. The kidneys of SHR-SP showed glomerular sclerosis, glomerular fibrosis, tubular casts, interstitial cell infiltration and vascular wall thickening or hyperplasia of the small arteries and arterioles. The severe glomerular sclerosis was mostly distributed in the inner and middle portions of cortex. Immunohistological study showed IgG, C3 and fibrinogen in the glomeruli and arterioles in SHR-SP. In captopril-treated SHR-SP, similar to SHR-SR, only minor histological changes were seen and there was no deposition of IgG, C3 or fibrinogen. No changes were seen in WKY. Thus, it was concluded that nephrosclerosis and cardiac hypertrophy in SHR-SP are prevented by captopril. The role of the renin-angiotensin and kallikrein-kinin systems in organ pathogenesis in SHR-SP is discussed.
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PMID:Prevention of nephrosclerosis and cardiac hypertrophy by captopril treatment of spontaneously hypertensive rats. 294

Hypertensive diabetic animal models have been developed by injecting streptozotocin (STZ) in neonatal stroke-resistant spontaneously hypertensive rats (SHRSR) and stroke-prone SHR (SHRSP) at the age of two days. After the treatment, the animals showed mild insulin deficiency and mild hyperglycemia at the age of three to four months. Diabetic nephropathy was produced particularly in STZ-treated SHRSR at the age of six months. The effect of neonatal STZ injection on hyperglycemia varied among normotensive Wistar-Kyoto rats (WKY), SHRSR, and SHRSP; SHRSR showed the highest glucose levels, SHRSP showed intermediate levels, and WKY was the lowest. All STZ-treated SHRSR showed glycosuria, while glycosuria was not observed in the treated SHRSP and WKY. Histologic study indicated that these strain differences were partly ascribed to differences in islet B-cell sensitivity to toxic effects of STZ. The development of hypertension was not accelerated in these SHRSR and SHRSP compared with respective nontreated controls. Since STZ-treated SHRSR develop mild diabetic symptom with hypertension and develop mild diabetic glomerulosclerosis, they are good models for studying vascular complications or other problems relating to the synergism between hypertension and diabetes mellitus.
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PMID:New establishment of hypertensive diabetic animal models: neonatally streptozotocin-treated spontaneously hypertensive rats. 360 Feb 85

Chronic glomerulonephritis (CGN) is responsible for 105 (1.16%) of all 9015 necropcies in a multi-specialized hospital but it occupies the third place after chronic pyelonephritis and diabetic glomerulosclerosis 9.20 per cent. In 91.4 per cent of the deceased of CGN arterial hypertension (AH) had been concomitant, with an average duration, according to anamnestic data, 6.28 years with a mainly light and moderate hypertrophy of left ventricle. Those that died of CGN without AH lived 9.20 years, on the average, wore than those with hypertension. In about 30 per cent of CGN with AH, the hypertension contributed to the lethal end prior to the terminal uremia--from cardiac insufficiency--25 per cent and cerebrovascular stroke 4.16 per cent. The significantly poorer atherogenesis in aorta and coronary and cerebral arteries is worth mentioning in case of CGN with hypertension as compared with the essential hypertension. (The deceased examined were not dialyzed). That atherogenesis is even poorer than hypertension of chronic pyelonephritis.
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PMID:[Incidence of chronic glomerulonephritis and its hypertonic terminal-stage syndrome and the severity of the cardiovascular changes among 9015 autopsied patients over 14]. 663 5

In 179 patients subjected to 186 renal transplants, 30 renal biopsies were performed due to the presence of a proteinuria over 3.5 g/24 h or due to a reduction in glomerular filtration rate. Six of these biopsies, coming from 5 patients, disclosed morphological alterations compatible with focal segmental glomeruloesclerosis. Five of these were due to recurrence of the primary disease (in four patients) and in all, massive proteinuria appeared from 1 to 23 days after transplantation. Two patients with three transplants, evolved to renal failure and required dialysis in a period 12 months as a mean. The third patient, developed a nephrotic syndrome without renal failure and died 14 months after the renal transplant due to a stroke. In the fourth patient, the nephrotic syndrome disappeared 38 days after the transplant and remained with minimal proteinuria until his last follow up visit two years later. The primary disease of the fifth patient is unknown; the nephrotic syndrome appeared 68 months after the transplant and remitted spontaneously in 2 months. The renal biopsy showed focal and segmental lesions with partial effacement of epithelial foot processes. It is concluded that focal segmental glomerulosclerosis recurrence in renal transplant occurs with early massive proteinuria and frequently leads to renal failure and graft loss in no more than two years.
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PMID:[Focal and segmental glomerulosclerosis in renal transplantation]. 773 12

This study was performed to examine the effects of blockade of the renin-angiotensin system on the development of hypertension and renal damage in stroke-prone spontaneously hypertensive rats (SHR-sp), using a non-peptide angiotensin II receptor antagonist, CV-11974. We examined changes in blood pressure, urinary protein excretion, creatinine clearance and renal morphology in CV-11974-treated SHR-sp rats and compared these variables with those in non-treated SHR-sp and Wistar Kyoto (WKY) rats, as well as in hydralazine-treated SHR-sp rats. CV-11974 lowered systolic blood pressure in a manner similarly to hydralazine (CV-11974 204 +/- 3, hydralazine 200 +/- 3, non-treated SHR-sp 284 +/- 9, WKY 155 +/- 5 mmHg), but reduced urinary protein excretion more than hydralazine (p < 0.01). There were no significant differences in creatinine clearance among experimental groups. The glomerulosclerosis index was greater in non-treated and hydralazine-treated SHR-sp rats than in CV-11974 treated SHR-sp and WKY rats (p < 0.01). Hydralazine-treated SHR-sp rats had a lower glomerulosclerosis index than the non-treated SHR-sp rats (p < 0.01). No significant differences were found in glomerulosclerosis index between CV-11974-treated SHR-sp and WKY rats. Tubular atrophy, tubular casts and interstitial fibrosis were observed in non-treated SHR-sp rats and, occasionally, in hydralazine-treated SHR-sp rats, but not in CV-11974-treated SHR-sp rats or WKY rats. These results indicate that the angiotensin II receptor antagonist was superior to hydralazine as far as renal protection was concerned. This suggests that renal damage in SHR-sp rats is associated not only with hypertension but also with activation of the renin-angiotensin system.
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PMID:Renal protective effects of angiotensin II receptor I antagonist CV-11974 in spontaneously hypertensive stroke-prone rats (SHR-sp). 788 3

Recent evidence suggests focal glomerulosclerosis may be analogous to atherosclerosis. To investigate the role of hypertension and hypercholesterolemia in the appearance of glomerular foam cells, 2, 6 or 9-month-old stroke-prone SHR (SHRSP) were fed the high fat cholesterol diet (2% cholesterol, 0.5% cholic acid, 7% lard, 0.2% methylthiouracil; HFC) for 4 weeks. Serum total cholesterol was significantly elevated in HFC. Form cells were observed in glomeruli of 6- and 9-month-old, but not 2-month-old SHRSP with dietary-induced hypercholesterolemia. The glomerular foam cells varied in quantity almost in parallel with the duration of severe hypertension. Glomeruli with foam cells prominently situated in juxtamedullary region. Foam cells were frequently seen in glomerular sclerotic area. These results suggest that hypertension rather than hyperlipidemia may be more important for glomerular deposition of lipid, especially in early lesions, and hyperlipidemia may play a role in the foam cells accumulation.
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PMID:[Study on the glomerular foam cells in stroke-prone SHR]. 851 96

Previous studies have demonstrated differences in the progression to glomerulosclerosis with the use of calcium channel blockers (CCB). The results with angiotensin-converting enzyme (ACE) inhibitors are more consistent. Moreover, only two studies have examined the combined effects of these drug classes on the development of glomerulosclerosis. The aim of the study presented here was to test the hypothesis that nonhypotensive doses of the combination (VT) of a nondihydropyridine CCB, verapamil (V), and an ACE-inhibitor, trandolapril (T), will slow the development of glomerulosclerosis better than either agent alone in stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were randomized to treatment in one of three groups with nonhypotensive doses of these agents; a fourth group served as control (C). The control rats developed significant increases in proteinuria compared with the other groups (C, 190 +/- 35 mg.kg-1.d-1 versus VT, 19 +/- 12 mg.kg-1.d-1; P < 0.05). This finding correlated with the degree of glomerulosclerosis (mean severity grading for C, 3.31 +/- 0.21 versus VT, 1.6 +/- 0.51; P < 0.05). Moreover, there was no significant reduction in arterial pressure between these groups (C, 282 +/- 5 versus VT, 259 +/- 13 mm Hg; P = 0.12). Despite persisting hypertension, the rise in proteinuria was also attenuated in both the V group (57 +/- 21 mg.kg-1.d-1) and the T group (43 +/- 24 mg.kg-1.d-1). However, compared with the control rats, kidney morphology was unchanged. Lastly, creatinine clearance was better preserved in the VT group compared with the control group (C, 0.57 +/- 0.01 versus VT, 0.74 +/- 0.06 mL.min-1.100 g-1; P < 0.05). It was concluded that the combination of nonhypotensive doses of VT attenuates the rise in proteinuria and progression to glomerulosclerosis. This study supports the concept that VT may have effects on the glomerulus that are independent of blood pressure reduction.
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PMID:Individual and combined effects of verapamil or trandolapril on attenuating hypertensive glomerulopathic changes in the stroke-prone rat. 873 2

Renal plasma flow (RPF), glomerular filtration rate (GFR), glomerular pathology and glomerular TGF-beta gene expression were examined in 12- and 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). These parameters were also examined in SHRSP treated with equihypotensive doses of angiotensin II receptor antagonist (CV-11974:CV) and hydralazine (Hyd) for 12 weeks. Twelve-week-old SHRSP showed a decrease in RPF and GFR, and an increase in filtration fraction (FF) and urinary protein excretion (UP) compared to WKY. CV normalized these parameters, whereas although Hyd showed improved levels they were not to the levels achieved by the WKY. Glomerular TGF-beta expression was increased 2.0-fold in 12- and 24-week-old SHRSP, and CV, but not Hyd, decreased it to the control levels of WKY. At 24 weeks old, SHRSP showed a higher glomerulosclerosis index (GI) than WKY. CV, but not Hyd, lowered the GI to the level of the WKY controls. These data indicate that renal hemodynamic changes are closely associated with an increased TGF-beta expression in SHRSP and that this condition is caused by angiotensin II.
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PMID:Involvement of angiotensin II in glomerulosclerosis of stroke-prone spontaneously hypertensive rats. 874 27


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