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)

Effects of angiotensin-converting enzyme inhibition (ACEI) on autonomic responses and hemodynamics in patients with congestive heart failure (CHF) subjected to isometric exercise have not been studied. We tested whether acute ACEI might influence the effects of isometric exercise in patients with CHF. In the first part of the study we showed that isometric exercise increased blood pressure in the control group and in the CHF group, whereas cardiac output increased only in the control group. Stroke volume remained unchanged in the control group, whereas it decreased significantly in CHF group. We next analyzed the effect of acute ACEI (5 mg ramipril) on the decrease in cardiac output during isometric stress in patients with CHF. During isometric exercise mean blood pressure and heart rate increased similarly in both groups. However, cardiac output decreased during placebo by -0.48 +/- 0.12 L/min (p < 0.01) but not during ACEI. Spectral analysis of blood pressure showed an increase (p < 0.01) in the high-frequency parasympathetic component from 7.3% +/- 3.6% to 18.1% +/- 9.5% after ACEI. norepinephrine plasma levels increased after isometric stress in the placebo group, whereas other hormones did not change. ACEI prevented the norepinephrine increase after isometric stress. Thus the decrease in cardiac output during isometric exercise in patients with CHF was prevented by acute ACEI. The effect of ACE inhibition may be related to reduced sympathetic activity.
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PMID:Angiotensin-converting enzyme inhibition, autonomic activity, and hemodynamics in patients with heart failure who perform isometric exercise. 861 23

The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied. Thirteen patients with mild to moderate essential hypertension completed this randomized, double-blinded, placebo-controlled, crossover study. After a three-week run-in period the patients entered three periods lasting four weeks each, wherein they were treated with placebo, spirapril, or hydrochlorothiazide. Blood pressure, hemodynamic variables (stroke volume, heart rate, cardiac output, index of contractility, and systemic vascular resistance), echocardiography (left ventricular mass), and Doppler-derived atrial to early (A/E)-ratio velocity time integrals (VTI) were measured at the end of each of the four periods. Spirapril lowered the A/E-ratio VTIs (0.57, 0.12-1.00) (P < 0.02) as compared with both placebo (0.80, 0.50-2.67) and hydrochlorothiazide (0.83, 0.44-1.25), and the drug normalized the A/E-ratio VTI in those patients with elevated values. The hemodynamic variables, left ventricular mass, and end-systolic wall stress were unchanged during all three treatments. There were no significant changes in mean blood pressure during the treatment periods. These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension. It thereby seems able to improve left ventricular diastolic function. The effect is not dependent upon changes in hemodynamic variables, blood pressure, left ventricular mass, or end-systolic wall stress.
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PMID:ACE inhibition with spirapril improves diastolic function at rest independent of vasodilation during treatment with spirapril in mild to moderate hypertension. 863 65

Primary human hypertension is a polygenic disorder. It is the prevalent cause of cardiovascular disease leading to cardiac failure, stroke, chronic renal failure and, ultimately to death. Several genes are involved in cardiovascular control mechanisms and their genetics are complex. Experimental models which are well defined are needed to clarify the role of individual genes. The generation of the hypertensive transgenic rat line TGR (mREN2)27 bearing the murine Ren-2 gene cloned from the DBA/2J mouse strain provides a monogenic model of hypertension in which the genetic basis (the additional renin gene) is known. These rats develop severe hypertension, which reaches 200 mm Hg and higher at 8 weeks of age in the heterozygous animal. Homozygous rats develop even higher blood pressures than heterozygous animals, which is paralleled by a higher mortality rate in homozygous rats. Animals develop pathomorphologic alterations which are characteristic for systemic hypertension. The transgenic rats are characterized by unchanged or even suppressed concentrations of active renin, angiotensin I (ANG I), ANG II, and angiotensinogen compared to transgene-negative littermates. In contrast, plasma levels of inactive renin (prorenin) are much higher in TGR (mREN)27 rats than in control animals. In the kidneys, renin is suppressed, probably mediated through negative feedback inhibition, in other tissues, especially in the adrenal gland, murine Ren-2 mRNA is expressed at very high levels. The cascade of pathophysiologic events which finally lead to hypertension is not fully understood in this rat model. Treatment with ACE inhibitors or angiotensin II receptor antagonists such as losartan is extremely efficient, which could mean that hypertension in this model is mediated through ANG II. Since the the renin-angiotensin system (RAS) in the kidneys is suppressed, other ANG II generating sites must be considered. This favors the concept of extrarenal RASs in this model.
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PMID:The hypertensive Ren-2 transgenic rat TGR (mREN2)27 in hypertension research. Characteristics and functional aspects. 873 83

Drug treatment with beta-blockers and diuretics in hypertensive men and women aged 70 and above confers highly significant and clinically relevant reductions in cardiovascular (especially stroke) morbidity and mortality. This satisfactory effect is not impaired by a low tolerability of the drugs used. Furthermore, treatment of elderly hypertensives with beta-receptor blockers and/or diuretics is cost-effective. In STOP-Hypertension the cost-effectiveness ratios were low and of the same magnitude for both men and women. The clinical implication of this is that blood pressure lowering therapy should be considered in elderly hypertensives, at least up until they are 80 years old. It should also be remembered that elderly patients often have other diseases than hypertension and that the drug treatment should be adjusted accordingly, e.g. by using a calcium antagonist or an ACE inhibitor, when indicated.
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PMID:Antihypertensive treatment in the elderly. 874 33

The 4 major classes of antihypertensive drugs are diuretics, beta-blockers, ACE inhibitors and calcium antagonists. The diuretics have recently regained prominence, largely due to the results of recent controlled trials. These trials in elderly patients demonstrated that low-dose diuretics were effective not only in preventing stroke but also in greatly reducing coronary-related events. Diuretics also decrease left ventricular mass more than the other major drug classes. In addition, they are the most effective drugs for use in combination therapy. By contrast, the safety of calcium antagonists has recently been questioned because of report of increased coronary morbidity and mortality. However, these adverse events may be restricted to the short-acting preparations, especially nifedipine, which causes cardiac stimulation. ACE inhibitors, like beta-blockers, are not only effective in reducing blood pressure, particularly when combined with a diuretic, but also improve angina and decrease postinfarction mortality. They also benefit congestive heart failure, stabilise or improve renal function in hypertensive and diabetic nephropathy and reduce albuminuria. Beta-Blockers are especially effective in reducing sudden cardiac death in patients with coronary heart disease, particularly in postinfarction patients. Final proof of the relative effectiveness of these drugs in preventing morbidity and mortality must await the outcome of large comparative trials currently under way. A recent national survey in the US found that more than 75% of hypertensive patients did not have their hypertension completely controlled. Possible reasons for this disturbing statistic are discussed along with suggestions for improvement.
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PMID:Current drug treatment and treatment patterns with antihypertensive drugs. 879 81

Hypertension should be detected and treated early in diabetic patients. It has a marked contribution to the morbidity and mortality of diabetic individuals due to both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. Prospective studies addressing the effects of antihypertensive regimens on the incidence of CHF, stroke, and coronary artery disease in the diabetic population are not available. We assume that the beneficial effects of therapy apply to both diabetic and nondiabetic subjects. Glycemic control and the lipid profile are major concerns when selecting an antihypertensive drug. Because hyperinsulinemia and insulin resistance have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may also become an important element in the selection of an antihypertensive agent. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer the most favorable metabolic profile when compared with diuretics and beta-blockers and should be used as the initial drugs in most clinical settings.
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PMID:Hypertension in diabetes mellitus. 879 6

Left ventricular remodelling after acute myocardial infarction, through long-term left ventricular chamber dilatation and increased wall stress can result in alteration of the contractile properties of the non-infarct zone, impairment of the systolic and diastolic performances of the left ventricle, and eventually congestive heart failure. Left ventricular remodelling is influenced by several factors, among which the role of systemic and tissue renin angiotensin systems is determinant. Pharmacological interventions on the renin angiotensin systems were shown to limit left ventricular remodelling and reduce mortality from acute myocardial infarction in rats and humans, although the results of some trials remain controversial. To date, the beneficial effects of ACE inhibitors have only been demonstrated in patients with a low residual ejection fraction. Recent observations of changes in left ventricular chamber dilatation and left ventricular wall hypertrophy occurring over the course of time after acute myocardial infarction allow better definition of the subset of patients who are at risk of progressive left ventricular dysfunction and congestive heart failure. An akinetic surface >20%, a left ventricular ejection fraction <0 x 40, an anterior location of the infarction, a stroke volume <31 ml.m(-2) during the acute phase, and persistent occlusion of the infarct-related artery are the most powerful predictors of late left ventricular function impairment. Some issues remain controversial, such as the optimal time for introducing ACE inhibitors after the onset of symptoms, the potential additive effects of ACE inhibitors given in conjunction with thrombolytic therapy, and the role of systemic angioplasty of the infarct-related artery.
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PMID:Left ventricular remodelling after acute myocardial infarction--solved and unsolved issues. 882 58

Hypertension is one of the most important cardiovascular risk factors. Without therapy hypertension leads to stroke, coronary heart disease with angina pectoris and myocardial infarction, kidney failure and/or peripheral vascular disease. The association between blood pressure and these cardiovascular complications can be demonstrated over the entire blood pressure range. The risk of stroke, myocardial infarction, renal failure or peripheral vascular disease increases with increasing blood pressure. Additional cardiovascular risk factors such as hyperlipidemia, smoking and diabetes involve a further increase in risk. Today hypertension can be effectively treated. To that end, diuretics, betablockers, ACE-inhibitors or calcium antagonists can be used. Alpha receptor antagonists and angiotensin AT1 receptor antagonists are also of value. The antihypertensive effectiveness of these drugs is comparable but may vary in individual patients. During antihypertensive therapy, a reduction in cerebrovascular and cardiac complications has been demonstrated for alpha methyldopa, diuretics and betablockers. In these studies, fatal and non-fatal strokes were reduced by 42%, while the reduction in cardiac events was less pronounced (14%). The reasons for this greater efficacy of antihypertensive therapy in the cerebral circulation are not clear. Other risk factors may be particularly important in the pathogenesis of coronary artery disease (e.g. genetic factors, hyperlipidemia and others) or hypertensive vascular changes in the coronary circulation may not be as reversible as they are in the cerebral circulation. The well documented correlation between stroke, myocardial infarction and hypertension, as well as the proven efficacy of antihypertensive therapy in preventing cardiovascular events, underscores the importance of effective and sustained blood pressure control in these patients.
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PMID:[Heart, brain and hypertension]. 884 9

Erythrocyte sodium-lithium countertransport (SLC) activity is elevated in essential arterial hypertension. With the growing attention to the genetic substrate of disturbed biochemical tests associated with essential arterial hypertension, we were particularly interested in the involvement of key genes for the regulation of SLC, possibly related to the pathophysiology of essential arterial hypertension. Consequently, the aim of the present study was to investigate SLC and its determining factors in essential hypertension. The influence of haptoglobin (Hp)-polymorphism, insertion/deletion polymorphism of angiotensin converting enzyme (ACE-I/D) and MNS blood group system on the regulation of SLC was studied. SLC activity was studied in a cross-sectional case-control study including 90 Caucasians: 60 patients with essential arterial hypertension who had been treated for at least 1 year and 30 normotensive controls. In essential hypertension, the SLC activity is significantly higher (P = 0.00005) than in controls. In normotensive patients, no differences in SLC are observed for the different polymorphisms studied. However, in the hypertensive group, SLC activity is higher (P = 0.003) in Hp 2-1 phenotype and independent of ACE-I/D genotyping and MNS blood group polymorphism. Multifactor analysis of variance in essential hypertension reveals significant (P = 0.001) differences in SLC activity for the presence or absence of Hp 2-1 phenotype and for body weight (P = 0.0003). Multivariate regression analysis shows the same parameters to be independent determining factors of SLC in essential arterial hypertension. No relation is found between SLC activity and target organ damage which includes coronary artery disease, peripheral arterial occlusive disease, left ventricular hypertrophy and cerebrovascular accident. We conclude that erythrocyte SLC activity is elevated despite pressure-lowering therapy. In essential arterial hypertension, individuals of Hp 2-1 phenotype show higher SLC activity than patients of other Hp-types, suggesting genetic heterogeneity of essential arterial hypertension. The presence or absence of Hp 2-1 phenotype is an independent determining factor of SLC activity whereas body weight codetermines SLC activity in essential hypertension.
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PMID:Genetic polymorphisms and erythrocyte sodium-lithium countertransport in essential hypertension. 893 Apr 12

The physiologic trophic factors growth hormone (GH) and insulin-like growth factor 1 (IGF-1) generally increase body weight and cardiac mass proportionately, and several studies suggest that both growth factors cause vasodilation and increased myocardial contractility. Established clinical benefits of ACE inhibitors can be explained, at least in part, by inhibition of cell hypertrophy, lowered systemic vascular resistance (SVR) and afterload, leading to reduction of progressive left-ventricular (LV) enlargement. An alternative approach would be to administer IGF-1 or GH to stimulate compensatory hypertrophy and reduce afterload by their vasodilator action, as well as through potential favorable effects on myocardial contractility. In our initial study in the rat myocardial infarction (MI) model, when IGF-1 was administered early (at 2 days) post-MI and continued for 2 weeks, body weight (BW) increased and LV weight/BW remained unchanged, the LV end-diastolic volume (EDV) and stroke volume increased (but not when normalized to BW), and the LV ejection fraction increased in rats with large infarctions. These findings suggested a beneficial rather than detrimental effect of such treatment, and we then studied the action of combined IGF-1 and GH starting after infarct healing at 4-weeks' post-MI. BW increased substantially and LVEDV/BW was lower in treated rats than in control rats, suggesting relatively less LV dilation with little remodeling in this setting; IGF-1/GH increased the cardiac output by 46%, systemic vascular resistance (SVR) fell and the cardiac index (CI) was significantly elevated in treated rats with a large MI. Recently, others have used the rat MI model to study the effects of 2-weeks' of GH started at 4-weeks' post-MI, as well as IGF/GH for 2-weeks in rats treated with an ACE inhibitor for 3-month's post-MI. In both studies, in conscious treated rats the BW increased, LV/BW was not different compared to the control rats, but the CI increased, SVR fell, and estimated LV dP/dtmax was significantly augmented. Preliminary data in our laboratory suggest that beneficial effects may also occur with GH administration in the setting of chronic angiotensin II receptor blockade (losartan) after MI in the rat. Thus, growth factor therapy appears to have favorable effects in heart failure early and late after MI in the rat. Additional cardiac hypertrophy occurs early after MI, but the later beneficial effects appear to relate primarily to systemic vasodilation, improved cardiac output, and enhanced myocardial contractility.
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PMID:The role of hypertrophy and growth factors in heart failure. 895 69


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