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

The spontaneously hypertensive rat and the stroke-prone spontaneously hypertensive rat are useful models for human hypertension. In these strains hypertension is a polygenic trait, in which both autosomal and sex-linked genes can influence blood pressure. Linkage studies in crosses between the stroke-prone spontaneously hypertensive rat and the normotensive control strain Wistar-Kyoto have led to the localization of two genes, BP/SP-1 and BP/SP-2, that contribute significantly to blood pressure variation in the F2 population. BP/SP-1 and BP/SP-2 were assigned to rat chromosomes 10 and X, respectively. Comparison of the human and rat genetic maps indicates that BP/SP-1 could reside on human chromosome 17q in a region that also contains the angiotensin I-converting enzyme gene (ACE). This encodes a key enzyme of the renin-angiotensin system, and is therefore a candidate gene in primary hypertension. A rat microsatellite marker of ACE was mapped to rat chromosome 10 within the region containing BP/SP-1.
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PMID:Chromosomal mapping of two genetic loci associated with blood-pressure regulation in hereditary hypertensive rats. 165 69

While antihypertensive therapy is considered to be an important clinical intervention in hypertensive patients, its effects on cardiac structure and function have not been intensely evaluated. In this study we tested the hypotheses that lowering blood pressure (BP) with the angiotensin I-converting enzyme inhibitor captopril, would: 1) normalize left ventricular mass and increase the cardiocyte mitochondria/myofibrils volume (Vmito/Vmyo) ratio; and 2) not compromise peak ventricular performance. We treated 16-week-old SHR and WKY with captopril (40-80 mg/kg) and hydrochlorothiazide (500 mg/l) via their drinking water. After six weeks of treatment peak cardiac performance was measured during rapid volume overload. Tissue samples from the left ventricular wall were analyzed by electron microscopy and stereology. Captopril lowered BP in SHR and WKY but had no affect on the left ventricular/body weight ratio. The only intracellular change in treated SHR was an increase in sarcoplasmic volume density. Treated WKY exhibited decreased midmyocardial mitochondrial volume density. At peak cardiac output, acceleration of flow and cardiac index were not affected by treatment. Stroke work at peak cardiac output was decreased in the treated groups due to a decrease in mean arterial pressure. In addition, captopril treatment resulted in a shift of the cardiac output (CO)-left ventricular end diastolic pressure (LVEDP) curves, such that LVEDP at peak cardiac output was approximately 50% less in the treated groups compared to their respective control groups. Although captopril was efficacious in lowering BP, it is suggested that lowering BP with this agent does not, at least within six weeks, lead to a reversal of hypertrophy or to a significant alteration in the volume densities of myofibrils and mitochondria. However, an important effect of this antihypertensive drug which may be of clinical significance, is that it leads to a leftward shift of the CO-LVEDP curve in both hypertensive and normotensive rats.
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PMID:Effects of captopril on left ventricular structure and function in SHR with established hypertension. 266 28

To determine whether chronic antihypertensive therapy prevents the progression of cardiac hypertrophy and the deterioration in cardiac performance observed in spontaneously hypertensive rats (SHR) with long-term hypertension, 14-month-old female SHR and normotensive American Wistar rats (NWR) were treated for 10 months with an inhibitor of angiotensin I-converting enzyme, captopril (2 g/liter of drinking water). Captopril reduced the marked left ventricular hypertrophy of 24-month-old SHR (untreated, 4.37 +/- 0.2 mg/g of body weight; treated, 3.01 +/- 0.1 mg/g; P less than 0.02) to levels observed in 6-month-old SHR. Treatment prevented the reductions in baseline and maximal aortic blood flows that occurred in SHR between ages 12 and 24 months yet had no effect on the blood flows of NWR. The diminished maximal stroke volume of untreated SHR was ejected from a significantly increased left ventricular end-diastolic volume, so that the ejection-fraction index was markedly reduced (24-month-old untreated NWR, 84 +/- 3%; untreated SHR, 56 +/- 5%; P less than 0.001). Therapy restores this index in SHR to normal (77 +/- 4%). The relationship between ejection-fraction index, and afterload was also normal in treated SHR. Thus, chronic therapy with captopril produced a marked regression of cardiac hypertrophy and prevented the deterioration of cardiac performance in SHR with long-standing hypertension.
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PMID:Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat. 621 29

We have previously identified a locus on rat chromosome 10 as carrying a major hypertension gene, BP/SP-1. The 100:1 odds support interval for this gene extended over a 35-centimorgan (cM) region of the chromosome that included the angiotensin I-converting enzyme (ACE) locus as demonstrated in a cross between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKY-0HD) rat. Here we report on the further characterization of BP/SP-1, using a congenic strain, WKY-1HD. WKY-1HD animals carry a 6-cM chromosomal fragment genotypically identical with SHRSPHD on chromosome 10, 26 cM away from the ACE locus. Higher blood pressures in the WKY-1HD strain compared with the WKY-0HD strain, as well as absence of linkage of the chromosome 10 region to blood pressure in an F2 (WKY-1HD x SHRSPHD) population suggested the existence of a quantitative trait locus, termed BP/SP-1a, that lies within the SHRSP-congenic region in WKY-1HD. Linkage analysis in the F2 (WKY-0HD x SHRSPHD) cross revealed that BP/SP-1a is linked to basal blood pressure, whereas a second locus on chromosome 10, termed BP/SP-1b, that maps closer to the ACE locus cosegregates predominantly with blood pressure after exposure to excess dietary NaCl. Thus, we hypothesize that the previously reported effect of BP/SP-1 represents a composite phenotype that can be dissected into at least two specific components on the basis of linkage data and congenic experimentation. One of the loci identified, BP/SP-1a, represents the most precisely mapped locus affecting blood pressure that has so far been characterized by random-marker genome screening.
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PMID:Dissection of a quantitative trait locus for genetic hypertension on rat chromosome 10. 756 16

1. Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a diet with fish meal as the protein source (fish diet) during the progressive stage of hypertension, and its effects on the activity of angiotensin I-converting enzyme (ACE) in serum and vascular tissues and on the aortic elastin content were studied. The effects of the antihypertensive drugs captopril and hydralazine were also studied. 2. Stroke-prone spontaneously hypertensive rats fed the fish diet showed a distinctly lower level (P < 0.05) of serum ACE activity than the control group fed a commercial stock chow. 3. ACE activity was enhanced in the SHRSP which was administered with captopril. 4. Serum ACE activity was similar in the SHRSP receiving the hydralazine treatment and the control group. 5. The thoracic aorta ACE activity was lowered more (P < 0.05) in the fish diet group and the captopril-treated group than in the control group. In the hydralazine-treated group however, the activity was similar to the control group. 6. The ratio of aorta weight to bodyweight was significantly lower (P < 0.05) in the fish diet group and the captopril-treated group than in the control group, but there was no difference in the hydralazine group. Higher levels of aortic elastin were observed in the drug-treated groups (P < 0.05). 7. No differences were seen between the fish diet and captopril-treated groups by electron-microscopy. 8. The results suggest that suppression of hypertrophy and ameliorations of reduction in elasticity of the vascular wall in the SHRSP fed a fish diet were due to inhibition of vascular tissue ACE activity.
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PMID:The vascular tissue angiotensin I-converting enzyme activity and aortic elastin content in stroke-prone spontaneously hypertensive rats fed fish diet. 798 75

The angiotensin I-converting enzyme (ACE) gene is found on the locus that has been linked to high blood pressure after sodium loading in rats, so in the present study we investigated the role of vascular ACE for the pathophysiology of hypertension in the corresponding parental strains, Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP), in basal conditions at different ages and after sodium loading. Blood pressure was already significantly enhanced in SHRSP from 4 weeks of age, and sodium loading induced an additional increase only in the hypertensive strain. In the aorta, basal ACE gene expression, analyzed by quantitative polymerase chain reaction, and ACE activity were similar in both strains, whereas mRNA levels were elevated in SHRSP after salt compared with WKY rats and correlated with an increase in enzymatic activity. In mesenteric arteries, ACE mRNA levels were significantly enhanced in SHRSP at all ages, although ACE activity was not different between the strains. These results were not modified after sodium loading. These data demonstrate that the level of ACE activity in plasma and vascular tissue can be controlled in a different manner within a rat strain and that in contrast to the soluble form, the membrane-bound ACE may be the one responsible for determining the vasoactive effects of angiotensin II. In addition, ACE undergoes a different regulation in vascular tissues of SHRSP compared with WKY rats, which might be involved in the regulation of blood pressure in these animals.
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PMID:Differential regulation of vascular angiotensin I-converting enzyme in hypertension. 808 33

The stroke-prone spontaneously hypertensive rat (SHR-SP) is an experimental model that has been widely used to investigate the potential preventive effects vs stroke and mortality of numerous antihypertensive agents. Among the latter, angiotensin I-converting enzyme inhibitors, angiotensin II AT1-receptor blockers and calcium antagonists have proven to be very effective. The mechanisms involved in their beneficial effects include limitation of the age-related alterations of large cerebral arteries' functional parameters, prevention of fibrinoid necrosis formation in cerebral arterioles and, to a lesser extent, limitation of the blood pressure rise.
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PMID:Antihypertensive drugs in the stroke-prone spontaneously hypertensive rat. 924 65

Plasma angiotensin I-converting enzyme (ACE) levels are different between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKYHD) rat. This interstrain variability in plasma ACE levels is independent of blood pressure and is genetically linked to the ACE gene. The present study explored the hypothesis of an interstrain variability of tissue ACE activity and ACE gene expression levels. Tissue ACE levels were studied by enzymic activity measurement in the membrane fraction, and ACE mRNA levels were quantified by solution hybridization-ribonuclease protection assay. In lung, heart, kidney, and duodenum, membrane-bound ACE activity and ACE mRNA amount were significantly higher in WKYHD rats compared with SHRSPHD rats. No difference was observed in the testis where a specific isoform of the enzyme is produced. Our results suggest that in addition to determine differential plasma ACE levels between the WKYHD and SHRSPHD strains, the interstrain genetic variability also determines differential ACE mRNA and membrane-bound enzyme levels in somatic tissues. This likely reflects a difference in the ACE gene expression due to genetically determined regulatory mechanisms operative in all somatic tissues.
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PMID:Interstrain differences in angiotensin I-converting enzyme mRNA and activity levels. Comparison between stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. 1036 81

1. The effect of food collagen, cattle bone collagen-derived (CBC) peptides, on ovariectomy induced increases in blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Long-term administration of CBC peptides to ovariectomized SHRSP suppressed the hypertension compared with ovariectomized SHRSP fed standard chow. 3. The CBC peptides showed an inhibitory activity (IC50 = 40 microg/mL) for angiotensin I-converting enzyme (ACE) in vitro. Furthermore, pre-incubation of CBC peptides with gastrointestinal proteases did not change this inhibitory activity of CBC for ACE. 4. These results indicate that CBC peptides may prevent increases in blood pressure in ovariectomized SHRSP by a possible mechanism of an inhibitory action against ACE.
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PMID:Antihypertensive effect of cattle bone collagen-derived peptides in ovariectomized stroke-prone spontaneously hypertensive rats. 1083 Dec 46

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been described in chromosome 17q23 of the human genome. Subjects with the genotype DD have markedly higher plasma ACE levels than those with genotype II; although ACE concentration in plasma is not rate-limiting for the production of angiotensin II, it has been suggested that the renin-angiotensin system may have an enhanced role in cardiovascular homeostasis in subjects with DD genotype or D allele. Meta-analysis confirmed the association of the D allele with an increased risk of myocardial infarction and stroke, but these relations are still uncertain with longevity and renal deterioration. Otherwise, I allele seems to be related with an improved response to physical training. The I/D polymorphism of the ACE gene is not a marker for any form of hypertension, though some conflicting results have been described. Nevertheless this polymorphism may have an influence on the antihypertensive response, particularly when using ACE inhibitors (ACEI). For example, blood pressure normalization with captopril in patients suffering from cardiac failure would be more effective in II genotype; conversely, both regression in left ventricular hypertrophy and improvement in diastolic filling would be greater after long-term treatment with enalapril in patients with essential hypertension and DD genotype. Conflicting results were also described using ACEI as a renoprotective therapy. This review therefore supports the justification for further evaluation in appropriately powered studies.
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PMID:Angiotensin I-converting enzyme gene polymorphism and drug response. 1109 39


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