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

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

Cardiac output (CO) and peripheral resistance (PR), the two major determinants of systemic arterial blood pressure (BP), are regulated principally by the adrenergic (ADR) and renin-angiotensin-aldosterone (RAA) systems. Antihypertensive medications ultimately decrease CO, PR, or both, by acting at various sites in the ADR and RAA pathways or affecting cardiovascular functions directly. Beta-ADR-receptor blockers decrease heart rate (HR) and stroke volume (SV) by preventing the cardiostimulating effects of catecholamines and inhibiting renin release. Alpha-ADR-receptor blockers prevent the vasoconstricting effects of catecholamines and reduce PR (afterload). Angiotensin-converting enzyme inhibitors (ACEI) block the formation of angiotensin, a potent peripheral vasoconstrictor and aldosterone releaser. Hence, ACEI cause a decrease in both PR and CO, the latter by preventing salt and water retention by aldosterone, thereby reducing plasma volume and venous return. Direct vasorelaxation and, thus, a fall in PR can be achieved by vasodilators. These include drugs (e.g. calcium antagonists) that prevent the entry of calcium ions into vascular smooth muscle cells, and others (e.g. nitrovasodilators) that boost the intracellular levels of vasodilating second messengers (e.g. cyclic GMP). Antihypertensives from different classes are often combined to improve the ratio between therapeutic and adverse effects.
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PMID:Therapies for perioperative hypertension: pharmacodynamic considerations. 848 May 1

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

Left ventricular hypertrophy (LVH), a target-organ response to chronic pressure or volume overload, is associated with its own independent risks of death in patients with hypertension. Numerous studies have shown that LVH increases the risk of coronary heart disease, congestive heart failure, stroke or transient ischemic attack, all-cause deaths, and sudden death. Although the mechanisms by which LVH develops are incompletely understood, the renin-angiotensin system may play an important role. All major classes of antihypertensive agents (calcium channel blockers, diuretics, beta-blockers, angiotensin-converting enzyme inhibitors) can cause LVH regression but not all to the same degree. Angiotensin-converting enzyme inhibitors may provide the most pronounced reduction in left ventricular mass per millimeter of mercury of blood pressure reduction. In addition, animal studies and human trials show promise for the regression of LVH with the use of angiotensin receptor blockers (ARBs). Because ARBs act specifically on the AT(1) receptor, angiotensin II can exert its favorable effects on cell growth inhibition through the AT(2) receptor. One small study that compared the ARB valsartan with atenolol found significant regression of LVH with the ARB by 8 months of treatment.
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PMID:Therapeutic options in minimizing left ventricular hypertrophy. 1061 82

Angiotensin-converting enzyme inhibitors (ACEIs) cause regression of hypertensive left ventricular hypertrophy (LVH) by reducing angiotensin II, increasing bradykinin, or both. The mechanisms of these cardioprotective effects remain controversial. The aims of this study were to determine whether the cardioprotective effects of ACEIs are mediated by reducing angiotensin II and whether ACEIs ameliorate the morphologic, physiologic, and biochemical changes in the hearts of stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were treated with hydralazine, captopril, or candesartan, an angiotensin II type 1 receptor (AT1R) antagonist, from age 12 to 24 weeks. We measured systolic blood pressure (SBP), left ventricular weight (LVW), left ventricular (LV) myocyte cross-sectional area (myocyte size), LV Interstitial collagen volume fraction (ICVF), perivascular collagen area/luminal area ratio (PVCA/LA), the medial area to luminal area ratio (MA/LA), the relative amount of V3 myosin heavy chain (MHCV3), and coronary reserve maximum (coronary flow max/ventricular weight (CFmax/VW)). These parameters were compared with those of untreated SHRSPs and Wistar-Kyoto rats (WKYs). SHRSPs exhibited decreased coronary reserve and LVH with an increase in myocyte size, PVCA/LA, MA/LA, and MHCV3 at 12 weeks of age. In addition to these changes, 24-week-old SHRSPs showed an increase in ICVF. The LVW, coronary reserve, myocyte size, PVCA/LA, ICVF, and MHCV3 of SHRSPs treated with captopril or candesartan all approached control values. In contrast, hydralazine decreased only ICVF. These results suggest that ACEIs regress LVH and normalize coronary reserve by modulating the effects of angiotensin II via AT1R on the induction of cardiomyocyte hypertrophy, perivascular fibrosis, and medial thickening of intramyocardial coronary arteries in SHRSPs. We concluded that these effects, in addition to the reduction of SBP, are important in causing the regression of LVH.
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PMID:Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats. 1077 52

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

Of the three major functional categories of cardiomyopathies (dilated, hypertrophic, and restrictive), the restrictive cardiomyopathies (RCMs) are the least common in the Western world, but unfortunately often are associated with the greatest morbidity and mortality. Infiltrative disease of the myocardium (often caused by amyloidosis) is a common cause of RCMs and has a significantly lower long-term survival rate when compared to cardiomyopathies of various other causes. Treatment of the RCM is, in general, difficult and often ineffective. Because of the abnormalities of diastolic filling that are characteristic of this condition, general measures to reduce venous and systemic congestion such as with the use of diuretics, are desirable but often result in an attendant reduction in stroke volume and cardiac output. Digoxin, calcium channel blocking drugs, and beta-adrenergic blocking agents are of limited value, although they may be used with benefit to control the heart rate response in the subgroup of patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors are generally ineffective in RCM. Targeted therapy directed against specific causal entities (such as the use of somatostatin analogues in carcinoid syndrome or iron chelation with desferrioxamine in hemochromatosis) may be more effective than simple symptomatic therapy. Differentiation of RCM from constrictive pericarditis is crucial, since constriction may be treated effectively by surgical removal of the thickened pericardium. A limited number of patients appear to have benefited from novel treatment strategies, such as autologous stem cell transplant in amyloidosis, balloon valvuloplasty of stenotic tricuspid or pulmonary valves in cardiac carcinoid syndrome, and cardiac transplantation. Truly effective therapy for RCM is generally lacking, and the best chance for optimizing the clinical outcome is early detection and aggressive medical treatment in an attempt to maintain the highest possible level of patient function for as long as possible.
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PMID:Restrictive Cardiomyopathy. 1109 47

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

Angiotensin-converting enzyme (ACE) inhibitors are now accepted as part of the routine management of patients with heart failure. Their use has been mandated in all the new major mortality trials to test the efficacy of beta-blockers in heart failure. Morbidity and mortality remain high in those with heart failure even with the benefits proven for both these groups of agents. In spite of the evidence for benefit of ACE inhibitors they are persistently used in lower doses in clinical practice than tested in the large-scale trials. This was so prevalent as to allow the conduct of a substantial study, the ATLAS trial, to compare high and low dose ACE inhibition. Its equivocal findings have allowed different interpretations. Clinical experience would suggest that starting with a low dose is appropriate but the dose should be titrated then without undue delay to the levels used in the trials wherever possible. The evidence for benefit with these drugs had been obtained largely in patients with impaired systolic function. However the AIRE study selected patients with clinical evidence of heart failure after myocardial infarction rather than with impaired systolic function. A substantial and long-term benefit was found from ACE inhibition. A cohort of patients had ventricular function assessed and as anticipated almost one half had preserved systolic function. Whilst the absolute benefit in lives saved was greater in the higher risk/low ejection fraction group, the relative risk reduction was not significantly different between those with preserved or impaired systolic function. The publication of the HOPE trial, although not a study of patients with heart failure, has clarified the situation considerably for those taking day to day care of patients. The HOPE study selected patients on the basis of high cardiovascular risk excluding those with known impaired systolic function. Although not an entry requirement for the study, ejection fraction was measured in a substantial majority and was above 40% indicating preservation of systolic function. The ACE inhibitor ramipril markedly reduced the combined end-point of cardiovascular death, stroke and myocardial infarction. Importantly there was a highly significant 20% risk reduction in the rate of myocardial infarction, a prospectively defined end-point, over the average four and a half year follow-up. Taken together with the retrospectively derived evidence from the heart failure trials there is now compelling evidence that the ACE inhibitors prevent myocardial infarction. The majority of patients with clinical heart failure have underlying ischaemic heart disease. Prevention of myocardial infarction and control of blood pressure are two key factors in the management of these patients irrespective of systolic ventricular function. The ACE inhibitors like the beta-blockers therefore have a pivotal role in their management. A challenge to current clinical trials is to determine whether these properties are shared to the same degree by the angiotensin antagonists or if even further gains in benefit can come from their combination. The neutral findings of the ELITE II study comparing the angiotensin antagonist, losartan, with the ACE inhibitor, captopril, have heightened interest in the on-going trials addressing these issues.
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PMID:ACE inhibitors in heart failure: an update. 1119 59

The novel antihypertensive drugs which have been discovered and developed in the latter half of the 20th century were investigated. Newly discovered or improved drugs are approved by the Ministry of Health and Welfare in Japan, and after then they become available for clinical use. We can follow the progress and trends of various new antihypertensive drugs by recording their years of approval. The four primary useful drugs for the treatment of hypertension were developed were introduced as listed in the following: 1. Antihypertensive diuretics: Thiazide and dihydrothiazide were first approved in 1958, and various related drugs including aldosterone antagonists and loop diuretics followed. 2. beta-Adrenergic-blocking drugs: Propranolol was approved in 1966 for heart diseases and for hypertension in 1970. Thereafter many related drugs were developed. 3. Calcium channel-blocking drugs: Nifedipine was approved, for heart disease in 1974 and for hypertension in 1981, and then many related drugs appeared. 4. Angiotensin-converting enzyme inhibitors: Captopril was approved in 1982 and thereafter various related drugs followed. The four categories of these drugs were selected as first choice drugs for the treatment of hypertension in 1988. The development of these excellent useful drugs affected the mortality rates of cerebrovascular diseases (e.g., apoplexy). The mortality curve reaches plateaued in 1963, peaked in 1965, and then declined rapidly. Antihypertensive diuretic drugs stop the rise of mortality, and beta-blocking drugs, Ca-antagonists and ACE-inhibitors promote rapid downward tendency.
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PMID:[Fifty years history of new drugs in Japan: the developments and trends of antihypertensive drugs]. 1164 Feb 8


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