Gene/Protein Disease Symptom Drug Enzyme Compound
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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

Keeping pre-transplant patients alive while waiting for a suitable donor to be found is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 18 transplant candidates with heart failure progression despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. Complete hemodynamic, echocardiographic, and neurohumoral studies were performed before and 24 h after intravenous enoximone infusion. Enoximone infusion increased cardiac index (1.78 +/- 0.45 l/min/qm vs. 3.04 +/- 0.83 l/min/qm; p < 0.001) and stroke volume index (22.33 +/- 9.45 ml/qm vs. 32.28 +/- 7.29 ml/qm; p < 0.05) and decreased wedge pressure (24.1 +/- 11.98 mmHg vs. 17.78 +/- 8.76 mmHg; p < 0.05) and systemic vascular resistance (1700.8 +/- 555.8 dyn x s x cm-5 vs. 952.8 +/- 384.0 dyn x s x cm-5; p < 0.001). Heart rate and mean arterial pressure were unchanged. Left ventricular ejection time (225.1 +/- 26.9 ms vs. 242.2 +/- 25.8 ms; p < 0.05) was increased, whereas other echocardiographic parameters were unchanged (left ventricular end-diastolic dimension, left ventricular end-systolic dimension, fractional shortening, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop of norepinephrine (936.7 +/- 443.2 pg/ml vs. 522.4 +/- 287.6 pg/ml; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low-dose enoximone therapy in pre-transplant patients: hemodynamic, echocardiographic, and neurohumoral findings. 809 24

The only antihypertensive treatment regimen with documented effect on morbidity and mortality from stroke and coronary heart disease is based on diuretics and/or beta-blockers. However, new antihypertensive drugs are now widely used. These compounds may also prevent cardiovascular complications, but, as yet, this has not been proven. The clinical trials of the 1990s such as STOP II, CAPPP and NORDIL will test whether antihypertensive treatment with ACE-inhibitors and calcium-blockers are more effective than diuretics and beta-blockers in preventing cardiovascular complications. Also, a large-scale study (HOT) is being undertaken to examine how far diastolic blood pressure should be treated, and whether a small dose of aspirin has a protective effect when combined with good control of blood pressure. These studies will hopefully lead to better guidelines for the future treatment of hypertension.
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PMID:[Can treatment of hypertension prevent myocardial infarction? New controlled clinical trials are proposed]. 809 58

Survival after acute myocardial infarction has been enhanced by treatment with thrombolytic agents, aspirin, and beta-adrenoceptor blockade. However there remains a substantial subgroup of patients who manifest clinical evidence of heart failure despite the first two of these treatments, and for whom beta-adrenoceptor antagonists are relatively or absolutely contraindicated. These patients have a greatly increased risk of fatal and non-fatal ischaemic, arrhythmic, and haemodynamic events. In this selected high-risk subset of patients we investigated the effect of therapy with the angiotensin converting enzyme (ACE) inhibitor rampiril, postulating that it would lengthen survival. 2006 patients who had shown clinical evidence of heart failure at any time after an acute myocardial infarction (AMI) were recruited from 144 centres in 14 countries. Patients were randomly allocated to double-blind treatment with either placebo (992 patients) or ramipril (1014 patients) on day 3 to day 10 after AMI (day 1). Patients with severe heart failure resistant to conventional therapy, in whom the attending physician considered the use of an ACE inhibitor to be mandatory, were excluded. Follow-up was continued for a minimum of 6 months and an average of 15 months. On intention-to-treat analysis mortality from all causes was significantly lower for patients randomised to receive ramipril (170 deaths; 17%) than for those randomised to receive placebo (222 deaths; 23%). The observed risk reduction was 27% (95 % Cl 11% to 40%; p = 0.002). Analysis of prespecified secondary outcomes revealed a risk reduction of 19% for the first validated outcome (i.e., first event in an individual patient)--namely, death, severe/resistent heart failure, myocardial infarction, or stroke (95% Cl 5% to 31%; p = 0.008). Oral administration of rampiril to patients with clinical evidence of either transient or ongoing heart failure, initiated between the second and ninth day after myocardial infarction, resulted in a substantial reduction in premature death from all causes. This benefit was apparent as early as 30 days and was consistent across a range of subgroups.
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PMID:Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. 790 9

Left ventricular damage by necrosis of myocardial tissue can lead to compromise of left ventricular function, to left ventricular volume increase and ultimately to development of heart failure. This sequence in the pathophysiology has been shown to be blunted by ACE inhibitors. Volume increase, however, can also be helpful in restoring stroke volume and ameliorate elevation of filling pressures. Furthermore, very early institution of ACE inhibition has failed to improve short-term mortality after myocardial infarction in one large trial. The aim of the ECCE trial therefore is, to investigate the early effects of the ACE inhibitor captopril on compromise of exercise capacity, thought to be a first measurable sign of developing heart failure. The ECCE trial is a randomized, seven-center investigation, studying the effects of ACE inhibition on oxygen uptake in a double blind, placebo controlled design in a group of 204 patients. Sample size was calculated on the basis of a pilot trial. The study design and first not unblinded data of 104 patients are presented. The population consists of predominantly male patients with mostly first myocardial infarction. They were admitted to hospital within five hours of onset of chest pain. End-diastolic volumes were normal, but ejection fraction was moderately compromised. ACE inhibition was started after the first day, but within 72 hours of onset of chest pain. After four and after twelve weeks, oxygen uptake was considerably below expected values and one third of the patients had severe compromise of exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experiences with ACE inhibitors early after acute myocardial infarction. Rationale and design of the German Multicenter Study on the Effects of Captopril on Cardiopulmonary Exercise parameters post myocardial infarction (ECCE). 812 22

Congestive heart failure is one of the most important causes of peripheral edema seen in clinical practice. Edema in congestive heart failure is the result of the activation of a series of humoral and neurohumoral mechanisms that promote sodium and water reabsorption by the kidneys and expansion of the extracellular fluid. These mechanisms, in concert with abnormal Starling forces such as increased venous capillary pressure and decreased plasma oncotic pressure, promote fluid extravasation and edema formation. The management of edema in congestive heart failure is designed to improve cardiac function and to inhibit the hormonal and neurohumoral pathways that promote edema. The combination of diuretics and vasodilators or angiotensin converting enzyme inhibitors and, in some cases, cardiac inotropic agents is highly effective in achieving these goals and providing significant symptomatic improvement in patients with edema secondary to congestive heart failure.
Heart Dis Stroke
PMID:Pathophysiology of edema in congestive heart failure. 815 85

It is well established that hypertensive patients benefit from drug treatment of their disorder. In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits, i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity. In all these studies beta-blockers and/or diuretics were used in comparison with placebo. Newer therapeutic alternatives have, however, at least theoretically, many advantages which could result in further improvements in prognosis. The initial Swedish Trial in Old Patients with Hypertension (STOP-Hypertension 1) was conducted in men and women aged 70-84 years. STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors (enalapril and lisinopril) or on calcium antagonists (isradipine and felodipine), using the PROBE design (Prospective, Randomised, Open, Blinded Endpoint evaluation). The primary aim will be to assess the effect on cardiovascular mortality. Statistical calculations indicate that 6,600 patients, followed for four years will be needed (2p < 0.05, power 90%) to obtain significance if there is a 25% difference between the new and the established therapy. Patients in primary health care (300 centres) will be included if their supine blood pressure is > or = 180/105 mmHg (and/or). Recruitment of patients started in September 1992 and so far more than 100 patients/week have been included.
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PMID:STOP-Hypertension 2: a prospective intervention trial of "newer" versus "older" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension. 818 Jul 29

Patients with mild to moderate hypertension require only a simple schedule of investigations, especially if there is a history of stroke or hypertension in first degree relatives. Tests are necessary to profile other cardiovascular risk factors and to detect target organ damage with only limited screening for secondary hypertension. Careful history, physical examination, repeated blood pressure measurements over months and measurements of body mass index, random cholesterol, routine blood chemistry and urinalysis using impregnated paper strips are all that are required. More detailed investigations can be reserved for special groups such as those with peripheral vascular disease or abnormal renal function before or after treatment with angiotensin converting enzyme inhibitors or significant proteinuria or hypokalaemia. Patients with essential hypertension who are smokers with lipid abnormalities may go on to develop superimposed renovascular disease. Severe hypertension at any age and especially if there is a reliable negative family history also merits special consideration. Resistance to antihypertensive treatment is more often due to non-compliance or non-steroidal anti-inflammatory drug use or alcohol abuse than to underlying secondary causes.
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PMID:Hypertension: investigation, assessment and diagnosis. 820 68

Necrosis of the femoral head and osteopenia were examined histopathologically in stroke-prone spontaneously hypertensive rats (SHRSPs) aged 6 to 36 weeks and compared with that of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Avascular necrosis of the femoral head was frequently observed, mainly in the young SHRSPs and SHRs (about 8 to 15 weeks of age). SHRSPs had the highest incidence of femoral head necrosis among the three strains. This necrotic change in the femoral head was considered to be secondary ischemia induced by angiospasm or arteriosclerosis, similar to the disorders observed in the brain, kidney, and heart in SHRSPs. However, the complication occurred in spite of treatment with antihypertensive agents (ACE inhibitor: enalapril, spirapril) even though other ischemic disorders such as brain hemorrhage and renal infarction were prevented, indicating that the femoral head necrosis in SHRSPs was not due to hypertensive complications induced by angiospasm or arteriosclerosis. Bone mineral density (BMD) of the femoral bone was significantly lower in SHRSPs, and the femoral heads in this strain were the most easily deformed by loads applied during compression tests. Histopathologically, the infarctions were encountered on the lateral side of the epiphysis, but no thrombi were observed. The lateral side of the epiphysis is the anatomic site where the weight load is greatest and the site where the nutritive artery enters. Our results strongly suggest that the coexistence of vulnerable bone matrix and physical weight load to the nutritive artery plays a crucial role in the occurrence of femoral head necrosis in SHRSPs, whether based on generalized or localized osteopenia.
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PMID:Femoral head necrosis and osteopenia in stroke-prone spontaneously hypertensive rats (SHRSPs). 826 49

After a brief synopsis of the classical antihypertensive drugs a survey is given of the newer therapeutics, such as calcium antagonists, ACE-inhibitors and alpha 1-adrenoceptor antagonists. Experimental drugs, such as imidazoline receptor agonists, renin inhibitors, angiotensin II receptor antagonists, alpha 2-adrenoceptor antagonists, potassium channel openers, ketanserin, endopeptidase inhibitors, and hybrid (multifactorial) drugs are discussed, with special attention for their modes of action. In spite of the ever increasing number of antihypertensive drugs and principles, the large scale of clinical evidence for a beneficial effect of long-term treatment (in particular with respect to protection against stroke) remains limited to diuretics and beta-blockers. In spite of this limitation it seems worthwhile to consider the newer antihypertensive drugs as well, especially for optimal treatment of the individual patient. The newer drugs may in particular offer special advantages in the presence of concomitant diseases, such as diabetes mellitus, hyperlipidaemia, angina pectoris or congestive heart failure.
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PMID:New avenues in antihypertensive drug treatment. 826 86


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