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

We examined whether the renal protective effect of the angiotensin I converting enzyme inhibitor enalapril in stroke-prone spontaneously hypertensive rats (SHRSP) is dose-related and associated with alterations in the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a stable breakdown product of prostacyclin. Enalapril maleate at 1.5, 5 and 15 mg/kg/day or vehicle was chronically administered to saline-drinking SHRSP (six per group) starting at 8.1 weeks of age. Vehicle-treated SHRSP developed severe hypertension, proteinuria and strokes (age at death, 14 +/- 1 weeks; mean +/- S.E.). Enalapril prolonged survival dose-dependently and reduced proteinuria; all SHRSP given 15 mg/kg/day lived beyond 23 weeks of age without evidence of stroke or proteinuria. There was no effect of enalapril at any dose on systolic arterial blood pressure in spite of variable levels of urinary protein excretion and onset of stroke in the different groups. Likewise, urinary 6-keto-PGF1 alpha and PGE2 excretion did not differ among the groups except for an increase in 6-keto-PGF1 alpha in the 15 mg/kg/day group at one week after initiation of enalapril therapy. These results are consistent with a dose-related renal protective action of enalapril in saline-drinking SHRSP that is not closely associated with sustained alterations in urinary excretion of renal vasodilatory PGs.
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PMID:The antiproteinuric action of enalapril in stroke-prone spontaneously hypertensive rats is unrelated to alterations in urinary prostaglandins. 154 1

In the present study we examined whether the angiotensin I converting enzyme inhibitor, captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age. In eight salt-loaded SHRSP treated with oral captopril (50 mg/kg/day) beginning at 8.4 weeks of age, systolic blood pressure was slightly but temporarily suppressed and then continued to rise; by 12 weeks of age systolic blood pressure reached levels of severe hypertension, 240 +/- 8 mm Hg, and did not differ from that of untreated SHRSP. No deaths or brain lesions were noted in captopril-treated SHRSP despite severe hypertension maintained through 26 weeks of age when the study ended. Captopril treatment prevented increases in urinary protein excretion (14 +/- 2 v 63 +/- 16 mg/day at 11.7 weeks of age, P less than .01) and the severe brain, renal, and cardiac vascular lesions observed in untreated SHRSP. When maintained on Stroke-Prone Rodent Diet and saline, plasma renin activity of untreated SHRSP surviving until 14.5 weeks of age was markedly increased (29.1 +/- 9.4 ng Ang I/mL/h) compared with either untreated SHRSP (9.2 +/- 2.5 ng Ang I/mL/h, P less than .01) or Wistar-Kyoto rats (3.5 +/- 1.0 ng Ang I/mL/h, P less than .01) maintained on standard diet and water.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic benefit of captopril in salt-loaded stroke-prone spontaneously hypertensive rats is independent of hypotensive effect. 193 Aug 50

The influence of chronic treatment with the angiotensin I converting enzyme (ACE) inhibitor enalapril on blood pressure, kidney function, and survival was examined in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP that were fed a Japanese rat chow plus a 1% NaCl drinking solution beginning at 7-8 weeks of age developed severe hypertension and stroke; 14 of 18 untreated control SHRSP died by 14 weeks of age and exhibited evidence of cerebrovascular lesions. When enalapril (15 mg/kg/day) was included in the drinking solution of 15 SHRSP, blood pressure was initially reduced by only a slight degree, whereas survival improved markedly; only one of 10 SHRSP died before the rest were killed at 18 to 21 weeks. The remaining five enalapril-treated SHRSP lived beyond 36 weeks and on histological examination exhibited no evidence of cerebrovascular lesions. Chronic enalapril treatment also prevented the greater urinary excretion of protein and severe renal lesions observed in untreated SHRSP but did not affect urinary salt and water excretion. In anesthetized rats, glomerular filtration rate and tubular reabsorption of water were lower in untreated control SHRSP when compared with enalapril-treated SHRSP. Mean arterial pressure was comparable in both groups. These data support a possible role for ACE inhibition in the prevention of stroke and maintenance of kidney function independent of any marked change in blood pressure of SHRSP. Whether the protective effects of ACE inhibition relate to reduced angiotensin II formation, increased tissue kinins, or another mechanism remains to be determined.
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PMID:Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats. 253 41

The renin inhibitor H77 and the angiotensin I converting enzyme (ACE) inhibitor captopril were compared in separate experiments with infusion of 5% dextrose as a control for the effects on plasma angiotensin II (Ang II) concentration, arterial pressure and cardiac function, measured by Swan-Ganz catheter, in conscious dogs. The effects of a high dose of H77 (10 mg/kg per h) were similar to those of high-dose captopril (6 mg/kg per h). Both reduced plasma Ang II concentration, systemic vascular resistance and arterial pressure; both increased the heart rate; both increased cardiac output but the change was significant only with captopril; neither affected stroke volume, pulmonary artery pressure or pulmonary vascular resistance; both reduced left and right atrial pressures. The similar pattern of effects for the two inhibitors suggests that the mechanism by which they act is the same--reduction in Ang II--and that the cardiovascular effects of H77 are not a specific action of the peptide that is unrelated to the reduction in plasma Ang II concentrations.
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PMID:Effects of the renin inhibitor H77 on angiotensin II, arterial pressure and cardiac function in conscious dogs: comparison with captopril. 266 15

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

The effects of long-term treatment with a novel angiotensin I converting enzyme (ACE) inhibitor, trandolapril, on ACE activity and cardiac function in rats with chronic heart failure (CHF) were examined and compared with those of captopril and enalapril. Left coronary artery ligation of rats resulted in decreases in mean arterial pressure, left ventricular systolic pressure, dP/dt, cardiac output and stroke volume indices, and increases in left ventricular end-diastolic pressure and systemic vascular resistance 12 weeks after the operation. A significant increase in ACE activity of the myocardium, but not that of serum or other tissues, was detected in the CHF rat 12 weeks after the operation. Oral treatment with ACE inhibitors (10 mg/kg/day captopril, 10 mg/kg/day enalapril or 3 mg/kg/day trandolapril) from the 2nd to 12th week, attenuated the changes in cardiac output and stroke volume indices, left ventricular end-diastolic pressure and systemic vascular resistance of the CHF rat. Treatment also attenuated the increase in the cardiac. ACE activity of CHF rats. A close relationship between the decrease in cardiac output index and the increase in cardiac ACE activity was detected. The results suggest that trandolapril, like other ACE inhibitors, exerts a beneficial effect on cardiac function in the CHF rat and that one of the mechanisms for this effect is attenuation of elevated cardiac ACE activity.
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PMID:Effects of trandolapril on cardiac angiotensin I converting enzyme activity in rats with chronic heart failure following myocardial infarction. 747 61

We have recently shown that the angiotensin I converting enzyme (ACE) gene is linked to NaCl-loaded blood pressure in the stroke-prone spontaneously hypertensive rat (SHRSP), and that high-NaCl loading selectively stimulates ACE in the aorta of SHRSP but not in normotensive Wistar-Kyoto (WKY) rats. We therefore investigated the relationship between cardiac ACE and the development of hypertension and left ventricular hypertrophy in response to normal- and high-NaCl diet in these rats. ACE mRNA and ACE activity were measured in left ventricular tissue after completion of hemodynamic characterization of the animals. While SHRSP rats increased blood pressure (P < 0.0001) and heart rate (P < 0.005) in response to high NaCl, blood pressure remained unchanged in WKY. Similarly, relative left ventricular weight increased only in SHRSP after high NaCl (P < 0.002). A significant two- to threefold increase of cardiac ACE mRNA and fourfold stimulation of ACE enzyme activity in response to high NaCl was found in both WKY and SHRSP rats (P < 0.005). The induction of ACE gene expression was significantly more pronounced in SHRSP compared to WKY (P < 0.02), whereas no significant strain differences in left ventricular ACE activity were found after either normal- or high-NaCl diet. Thus, arterial blood pressure and left ventricular weight remained unchanged in the WKY rats despite the activation of left ventricular ACE activity after high-NaCl exposure. These results demonstrate that left ventricular ACE activity is equally upregulated in response to high-NaCl in the normotensive and hypertensive strain, independently from the development of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction of cardiac angiotensin I-converting enzyme with dietary NaCl-loading in genetically hypertensive and normotensive rats. 767 Sep 28

Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a diet containing docosahexaenoic acid (DHA)-enriched Euglena glacilis (DHA-Euglena) as the protein source from 5 weeks of age. The effects on endothelial functions were investigated by perfusion experimentation using mesenteric vasculature, and compared with the effects of antihypertensive drugs. (1) At 13 weeks of age, SHRSP fed the DHA-Euglena diet showed an average blood pressure of 220 mmHg, which was 20 mmHg lower (p < 0.05) than that in the control group, while SHRSP of the captopril-treated group (angiotensin I converting enzyme inhibitor: 200 mg/L drinking water) and hydralazine-treated group (vasodilator: 60 mg/L drinking water) showed marked hypotensive effects with blood pressures of 150-160 mmHg and 180-190 mmHg, respectively. (2) The constriction response to norepinephrine (NE) was lower (p < 0.01) in the mesenteric vasculature isolated from the DHA-Euglena-treated SHRSP than in that from the control group. (3) When the mesenteric vasculature isolated from 13-week-old SHRSP fed the DHA-Euglena diet was perfused with an acetylcholine solution (10(-6) M) in the presence of NE (8 x 10(-6) M), the relaxation rate was 81%, which was higher (p < 0.01) than that in the control group (61%). Among the antihypertensive-treated groups, the captopril-treated group gave nearly the same relaxation rate as the DHA-Euglena diet group, while the hydralazine-treated group indicated a slightly lower rate (65%). At 18 weeks of age, the endothelium-dependent relaxation of SHRSP in the control group was further reduced (28%), but in both the DHA-Euglena diet group and antihypertensive-treated groups, the relaxation rates were not substantially different from the levels at 13 weeks of age. Reduction of the endothelium function in SHRSP occurs due to aging and blood pressure elevation. However, by improving nutritional conditions by the feeding of a DHA-Euglena diet, the endothelial functions were protected without a fall in blood pressure unlike antihypertensive drugs. It is hence considered that nutritional improvement helps maintain a sound architecture for the vascular wall, thereby leading to the suppression and delay of onset of cerebrovascular diseases, and subsequently to the prolongation of life-span.
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PMID:Suppressive action of docosahexaenoic acid enriched-Euglena on reduction of endothelium-dependent relaxation in stroke-prone spontaneously hypertensive rats (SHRSP). 921 94

Left ventricular remodeling in hypertension is associated with cardiac interstitial and perivascular collagen deposition. The dual angiotensin I converting enzyme/neutral endopeptidase inhibitor omapatrilat (also called vasopeptidase inhibitor) improves left ventricular remodeling in experimental heart failure. We hypothesized that omapatrilat would induce regression of cardiac and vascular fibrosis in hypertension. We, therefore, investigated the effect of omapatrilat on collagen deposition in heart and aorta of stroke-prone spontaneously hypertensive rats (SHRSP). Twenty-week-old normotensive Wistar-Kyoto (WKY) rats, untreated SHRSP, and SHRSP treated with omapatrilat (40 mg/kg per day, orally) for 10 weeks were investigated. Collagen in the heart and the descending thoracic aorta was stained with Sirius red. After 10 weeks, systolic blood pressure (BP) was significantly (P < .01) reduced in omapatrilat-treated versus untreated SHRSP. Interstitial collagen density was significantly decreased in the subendocardial myocardium (to 2.71 +/- 0.24% v 4.12 +/- 0.30%, respectively, P < .05) and in the midmyocardium of omapatrilat-treated versus untreated SHRSP (to 3.01 +/- 0.25 v 4.19 +/- 0.17% respectively, P < .05). Perivascular collagen was significantly (P < .05) decreased in the subepicardial, mid-myocardial and, subendocardial regions of the myocardium of omapatrilat-treated versus untreated SHRSP. Aortic collagen content decreased in omapatrilat-treated versus untreated SHRSP (to 36.1 +/- 2.8 v 58.8 +/- 6.1 x 10(3) microm2/mm section, respectively, P < .05). In conclusion, in addition to being a potent antihypertensive agent, omapatrilat significantly improves cardiac and vascular fibrosis in SHRSP.
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PMID:Effect of ACE/NEP inhibition on cardiac and vascular collagen in stroke-prone spontaneously hypertensive rats. 1171 Jul 87

Year to year obesity prevalence, reduced physical activities, bad habits/or stressful lifestyle, and other environmental and physiological impacts lead to increase in diseases such as coronary heart disease, stroke, cancer, diabetes, and hypertension worldwide. Hypertension is considered as one of the most common serious chronic diseases; however, discovery of medications with high efficacy and without side effects for treatment of patients remains a challenge for scientists. Recent trends in functional foods have evidenced that food bioactive proteins play a major role in the concepts of illness and curing; therefore, nutritionists, biomedical scientists, and food scientists are working together to develop improved systems for the discovery of peptides with increased potency and therapeutic benefits. This review presents a recent research carried out to date for the purpose of isolation and identification of bioactive hydrolyzates and peptides with angiotensin I converting enzyme inhibitory activity and antihypertensive effect from animal, marine, microbial, and plant food proteins. Effects of food processing and hydrolyzation conditions as well as some other impacts on formation, activity, and stability of these hydrolyzates and peptides are also presented.
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PMID:Recent Research in Antihypertensive Activity of Food Protein-derived Hydrolyzates and Peptides. 2503 95


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