Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study hypothesizes that endothelin-1 induces renal damage by increasing expression of growth/inflammatory factors, important in renal fibrosis. Male stroke-prone spontaneously hypertensive rats (SHRSPs) (8-weeks, n = 24) were randomized into three groups: control group, high-salt group (4% NaCl), and salt plus an endothelin A receptor antagonist, BMS 182874 (40 mg/kg/d). After 20 weeks treatment, rats were killed. Messenger RNA (mRNA) expression of renal preproendothelin-1, endothelin A and B receptors, and procollagen I and III was evaluated by reverse transcription polymerase chain reaction. Expression of transforming growth factor (TGF)-beta1 and basic fibroblast growth factor (bFGF) was determined by immunoblotting. Matrix metalloproteinase-2 (MMP-2) activity was measured by zymography. In salt-loaded SHRSPs, preproendothelin-1 mRNA expression was increased 1.6-fold, and endothelin A receptor mRNA expression was decreased (70% of control). Salt-loaded SHRSPs had increased renal expression of TGF-b1 and procollagens. MMP-2 activity was augmented fivefold. BMS decreased (p < 0.01) expression of TGF-beta1, bFGF, and procollagen I and reduced MMP-2 activity. Thus severe hypertension and renal dysfunction in salt-loaded SHRSPs are associated with increased expression of renal endothelin-1, growth factors, and collagen. BMS treatment alleviated these effects, suggesting that nephroprotection by endothelin A receptor blockade is mediated by normalizing expression of growth factors, reducing extracellular matrix deposition, and decreasing MMP activity.
 ...
PMID:Endothelin A receptor blockade decreases expression of growth factors and collagen and improves matrix metalloproteinase-2 activity in kidneys from stroke-prone spontaneously hypertensive rats. 1202 84

This paper reviews literature data about non-pharmacological treatment of hypertension in women. A reduction in salt intake, an increase in physical activity and body weight reduction have been clearly demonstrated to be effective in reducing blood pressure values in women. Other lifestyle changes have been investigated in past years, but the results are still debated. A 4-8% body weight reduction causes an average 3 mmHg blood pressure decrease. However, many women tend to regain the weight (weight cycling), and in this case an increase of blood pressure can be observed. Older women are less responsive to low-calorie diets. Sodium restriction is effective in a dose-dependent way. The main problem is that good compliance is difficult to obtain. Salt substitutes may be helpful. Regular physical activity can reduce blood pressure by at least 5/3 mmHg, while walking for less than 2 h per week can reduce the risk of stroke by 50%. Data on coffee drinking are less conclusive even if there is evidence that the effect on blood pressure is greater at increasing levels of blood pressure. The reduction of alcohol intake, an increase in fibers and an increase in unsaturated fatty acids are well known tools to improve blood pressure control. Within unsaturated fatty acids, olive oil seems to be particularly helpful since it is able to produce significant blood pressure reductions, which are greater than those observed with sunflower oil.
 ...
PMID:Non-pharmacological treatment of hypertension in women. 1218 54

1. We showed that a nutritional factor was able to attenuate the development of hypertension and its related diseases in stroke-prone spontaneously hypertensive rats (SHRSP). In the present study, the effect of Wakame, an edible brown seaweed, on the development of stroke was examined in SHRSP. 2. We studied the treatment with 5% (w/w in a diet) Wakame powder in salt-loaded (0.5% NaCl in drinking water) SHRSP. Salt-loaded animals treated with 5% cellulose or kaolin were used as controls. Wakame significantly delayed the development of stroke signs (P < 0.05) and significantly improved the survival rate of salt-loaded SHRSP (P < 0.05). There was no significant difference in the elevation of blood pressure among the three groups during the observation period. 3. We isolated fucoxanthin, a carotinoid, from Wakame powder and studied its preventive effect on ischaemic cultured neuronal cell death. Fucoxanthin significantly attenuated neuronal cell injury in hypoxia and re-oxygenation (P < 0.05). 4. Based on these results, we conclude that Wakame has a beneficial effect on cerebrovascular diseases in SHRSP, independent of hypertension. It is possible that fucoxanthin in Wakame may have a preventive effect against ischaemic neuronal cell death seen in SHRSP with stroke.
 ...
PMID:Effect of Undaria pinnatifida (Wakame) on the development of cerebrovascular diseases in stroke-prone spontaneously hypertensive rats. 1254 52

Renin-angiotensin-aldosterone system blockade has been shown to protect against renal damage in salt-supplemented, stroke-prone spontaneously hypertensive rats (SHRsp). Based on intermittent tail-cuff blood pressure (BP) measurements, it has been claimed that such protection is BP-independent and mediated by a blockade of the direct tissue-damaging effects of angiotensin and/or aldosterone. BP radiotelemetry was performed for 8 weeks in approximately 10-week-old male SHRsp who received a standard diet and either tap water (n=10) or 1% NaCl to drink. Saline-drinking SHRsp were either left untreated (n=12), received enalapril (50 mg/L) in drinking fluid (n=9), or had subcutaneous implantation of time-release 200-mg pellets of aldactone (n=10). The average systolic BP (mean+/-SEM) during the final 3 weeks was significantly higher (P<0.05) in untreated saline-drinking (215+/-6 mm Hg) SHRsp but not aldactone-treated (198+/-4 mm Hg) or enalapril-treated treated SHRsp (173+/-1 mm Hg), as compared with tap water-drinking SHRsp (197+/-3 mm Hg). Histological renal damage scores at 8 weeks paralleled the BP in all groups, with an excellent correlation (r=0.8, P<0.001, n=41). Moreover, a renal damage score of >5 was only observed in SHRsp whose average systolic BP during the final 3 weeks exceeded 200 mm Hg, indicating a threshold relation with BP. These data show that protection by renin-angiotensin-aldosterone system blockade in this model is BP-dependent and mediated by preventing the severe increases in BP seen in untreated salt-supplemented SHRsp and further underscore the limitations of interpretations based on conventional tail-cuff BP measurements.
 ...
PMID:Renoprotection by ACE inhibition or aldosterone blockade is blood pressure-dependent. 1257 79

1. Homozygous deletion of the pro-atrial natriuretic peptide (Nppa) gene (ANP-/-) has been associated with both cardiac hypertrophy and salt-sensitive hypertension in mice, suggesting that cardiac hypertrophy in ANP-/- mice may be related, at least in part, to increased afterload. 2. To test the hypothesis that cardiac hypertrophy in ANP-/- mice is independent of blood pressure, male ANP-/- and wild-type ANP+/+ mice were fed a low (0.05%) or basal (0.55%) NaCl diet. Five weeks later, mean arterial pressure (MAP) was measured in conscious mice; the whole heart, atria, left and right ventricles (LV and RV, respectively), brain, lung, kidney, liver and spleen were weighed and fixed for histological analysis. Separate groups of mice were subjected to echocardiographic examination under tribromoethanol anaesthesia. 3. Mean arterial pressure and atrial, LV and RV mass were greater in ANP-/- mice than in ANP+/+ mice fed the basal salt diet. Salt depletion equalized MAP in the two genotypes, but did not alter the relative cardiac hypertrophy in ANP-/- mice. The ANP-/- mice had significant LV cardiomyocyte hypertrophy when fed either basal or low-salt diets. 4. Left ventricle chamber dimensions did not differ between genotypes, but were significantly reduced in mice fed the low-salt diet; LV posterior wall and septal thickness were greater in ANP-/- than ANP+/+ mice and were not altered by diet, indicating a concentric pattern of LV hypertrophy in ANP-/- mice. Left ventricle function (cardiac output, stroke volume, ejection fraction, circumferential wall stress and velocity of circumferential wall shortening) did not differ between strains on either diet; circumferential wall stress was reduced in the low-salt groups; other functional parameters were not altered by diet. 5. These findings indicate that ANP deletion results in cardiomyocyte hypertrophy and biventricular hypertrophy independent of blood pressure, supporting the concept that ANP has direct antihypertrophic effects in the heart.
 ...
PMID:Pressure-independent enhancement of cardiac hypertrophy in atrial natriuretic peptide-deficient mice. 1285 24

Angiotensin-converting enzyme inhibitors and aldosterone receptor antagonists ameliorate malignant nephrosclerotic lesions of thrombotic microangiopathy in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHRSP) without controlling hypertension. This suggests that angiotensin II (Ang II) and/or aldosterone (ALDO) plays a critical role in renal injury in this model. For evaluating their relative roles in the pathogenesis of thrombotic microangiopathy, SHRSP were adrenalectomized and infused with vehicle, Ang II, or ALDO or were sham-operated for adrenalectomy (SHAM). Saline-drinking rats were assigned to one of four groups: SHAM, adrenalectomy, adrenalectomy + Ang II (25 ng/min, subcutaneously), or adrenalectomy + ALDO (40 micro g/kg per d, subcutaneously). All SHRSP received dexamethasone (12 micro g/kg per d, subcutaneously). Adrenalectomy did not show changes in body weight, plasma creatinine, sodium and potassium, and daily urinary sodium and potassium excretion; did not prevent hypertension but prevented proteinuria (12 +/- 1 versus 49 +/- 3 mg/d; P < 0.01); and abrogated thrombotic microangiopathy and decreased plasma aldosterone (<16 versus 710 +/- 91 pg/ml; P < 0.001) compared with SHAM. Systolic BP in adrenalectomy + Ang II and adrenalectomy + ALDO (238 +/- 8 and 241 +/- 9 mmHg, respectively) was similar to SHAM. Despite Ang II infusion, proteinuria (17 +/- 9 mg/d) and thrombotic microangiopathy and plasma aldosterone (18 +/- 18 pg/ml) remained low but daily urinary excretion of sodium and potassium were not different from adrenalectomy + ALDO. Adrenalectomy + ALDO showed plasma aldosterone levels of 735 +/- 147 pg/ml; plasma potassium was lower; plasma creatinine and proteinuria (78 +/- 7 mg/d) were greater and thrombotic microangiopathy lesions were comparable to SHAM. These results demonstrate a pivotal role for aldosterone in the development of thrombotic microangiopathy, independent of hypertension.
 ...
PMID:Aldosterone plays a pivotal role in the pathogenesis of thrombotic microangiopathy in SHRSP. 1287 52

Salt-supplemented stroke-prone spontaneously hypertensive rats (SHRsp) develop more severe hypertension-induced renal damage (HIRD) compared with their progenitor SHR. The present studies were performed to examine whether in addition to increasing the severity of hypertension salt also enhanced the transmission of such hypertension to the renal vascular bed in the SHRsp. "Step" and "dynamic" renal blood flow (RBF) autoregulation (AR) were examined in approximately 12-wk-old SHR and SHRsp after 3-5 days of an 8% NaCl diet. During step AR under anesthesia (n = 8-11), RBF was significantly higher in the SHRsp at all perfusion pressures (P < 0.01), but AR capacity was not different. Similarly, in separate conscious chronically instrumented rats (n = 8 each), both blood pressure (BP) and RBF were modestly but significantly higher at baseline before salt in the SHRsp (P < 0.05). However, transfer function analysis did not show significant differences in the admittance gain parameters. However, after 3-5 days of salt, although average BP was not significantly altered in either strain, RBF increased further in the SHRsp and there was a significantly greater transfer of BP into RBF power in the SHRsp. This was reflected in the significantly higher admittance gain parameters at most frequencies including the heartbeat frequency (P < 0.05 maximum). These differential hemodynamic effects of salt have the potential to enhance BP transmission to the renal vascular bed and also contribute to the more severe HIRD observed in the salt-supplemented SHRsp.
 ...
PMID:Differential effects of salt on renal hemodynamics and potential pressure transmission in stroke-prone and stroke-resistant spontaneously hypertensive rats. 1582 45

Reactive oxygen species (ROS) are elevated in humans with hypertension many of which develop end-stage renal disease (ESRD), and antioxidant capacity is decreased. About one-half of essential hypertensives have a salt-sensitive type of hypertension, and the amount of renal damage that occurs in salt-sensitive hypertensives greatly exceeds that of non-salt-sensitive hypertensives. Antioxidant therapy can improve cardiovascular outcomes in humans but only if sufficient doses are used. Salt-sensitive hypertensive animal models, especially Dahl salt-sensitive rats, have been used to investigate the relationship between hypertension, ROS and end-stage renal damage. In experimental salt-sensitive hypertension, ROS increase and significant renal damage occur. In the Dahl salt-sensitive (S) rat on high Na for 3 weeks, renal damage is mild, renal levels of superoxide dismutase are decreased, and treatment with Tempol reduces arterial pressure. In the Dahl S rat on high Na for 5 weeks, renal damage is severe, GFR and renal plasma flow are decreased, and renal superoxide production is high. Treatment with vitamins C and E decreases renal superoxide production and renal damage and prevents the decrease in renal hemodynamics. Antioxidant treatment reduces arterial pressure, aortic superoxide production and renal inflammation in DOCA-salt rats, and decreases blood pressure and aortic superoxide release and increases bioactive nitric oxide in SHR stroke-prone rats. In conclusion, in both human and experimental salt-sensitive hypertension, superoxide production and renal damage are increased, antioxidant capacity is decreased, and antioxidant therapy can be helpful.
 ...
PMID:Oxidative stress and antioxidant treatment in hypertension and the associated renal damage. 1595 81

Relaxins are members of the insulin peptide superfamily. Previous evidence has shown that relaxin pretreatment reduces cortical infarct size in anesthetized, male rats receiving permanent middle cerebral artery occlusion (MCAO). Therefore, the current study was designed to determine if estrogenic mechanisms or nitric oxide production are involved in mediating this relaxin-induced neuroprotection. In separate groups of rats (n=4-6), the following drugs were injected directly into the cortex 30 min prior to MCAO: (a) relaxin, (b) relaxin and estrogen, and (c) relaxin and an estrogen receptor antagonist (ICI 182,780). To investigate the involvement of nitric oxide, relaxin or relaxin and an inhibitor of endothelial nitric oxide synthase (L-NIO) were injected i.v. 30 min prior to MCAO. Saline-treated rats (both intracortical (i.c.) and intravenously (i.v.)) served as controls. Brains were harvested 4h post stroke, coronally sectioned using a brain matrix and stained using 2,3,5-triphenoltetrazolium chloride (TTC). Digital photographs were taken of brain sections and the ratio comparing the area of the infarct to the area of the ipsilateral hemisphere was calculated. Mean ratios were compared using ANOVA and Tukey's test. Intracortical and intravenous relaxin pretreatment significantly reduced the infarct area in the cortex by 33.7 and 58.6%, respectively compared to saline-treated controls. This effect was not dependent on an interaction with estrogenic receptors as co-injection of relaxin and ICI 182,780 did not reverse this effect. However, inhibition of nitric oxide synthase significantly reduced the relaxin-mediated neuroprotection suggesting that relaxin may induce the endothelin-NOS cascade in cerebral vasculature causing vasodilation and improved perfusion of neural tissue.
 ...
PMID:Relaxin-induced reduction of infarct size in male rats receiving MCAO is dependent on nitric oxide synthesis and not estrogenic mechanisms. 1623 54

In current diets, the level of sodium is very high, whereas that of potassium, calcium, and magnesium is low compared with the level in diets composed of unprocessed, natural foods. We present the biologic rationale and scientific evidence that show that the current salt intake levels largely explain the high prevalence of hypertension. Comprehensive reduction of salt intake, both alone and particularly in combination with increases in intakes of potassium, calcium, and magnesium, is able to lower average blood pressure levels substantially. During the past 30 years, the one-third decrease in the average salt intake has been accompanied by a more than 10-mm Hg fall in the population average of both systolic and diastolic blood pressure, and a 75% to 80% decrease in both stroke and coronary heart disease mortality in Finland. There is no evidence of any harmful effects of salt reduction. Salt-reduction recommendations alone have a very small, if any, population impact. In the United States, for example, the per capita use of salt increased by approximately 55% from the mid-1980s to the late 1990s. We deal with factors that contribute toward increasing salt intakes and present examples of the methods that have contributed to the successful salt reduction in Finland.
 ...
PMID:Sodium intake and hypertension. 1704 32


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