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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A differential therapy of congestive heart failure requires the identification of the different stages of myocardial damage consequent to the underlying heart disease and the individual adaptive response to it. Because of their different load dependence, it is important to recognize the independent contribution of systolic and diastolic dysfunction in congestive heart failure. The vertical displacement of the diastolic pressure-volume loop is associated with a reduced therapeutic range. Reducing preload may limit the degree of diastolic filling necessary to fill a noncompliant heart and limit active myocardial stretch. The final outcome of any disorder is either to comprise cardiac filling, emptying, or both. When the end-stage is reached, only modification of excessive neurohormonal responses to heart failure remains. Efforts are necessary to avoid substances able to support the maladaptation. The rational use of vasodilator therapy in congestive heart failure is based on the concept that peripheral circulatory mechanisms overshoot, and may thereby act to exacerbate the heart failure. As important as it is to modify late neurohormonal responses, it is even more important to intervene at an earlier stage to reduce the degree of irreversible myocardial damage. Further studies have to prove the potential benefits of ACE-inhibitors in patients with mild heart failure in order to prevent or delay the progress of the disease.
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PMID:[Cardiac and extracardiac parameters as principles in differential therapeutic considerations for decreasing pre- and afterload]. 306 43

Molecular genetics is playing an increasing role in the diagnosis, treatment, and prevention of cardiac disease. Moreover, most of the genes that may cause cardiac disease or predispose an individual to cardiac disease are anticipated to be identified within the next 10 years. Several genes with risk for heart disease have been identified, such as the ACE genotype DD. Replacement gene therapy as well as use of promoter-specific drugs to act on genetic regulatory elements will encompass the future treatment of cardiovascular disease. This article provides a summary of the potential roles of genetic screening for cardiac risk factors and genetic interventions in cardiovascular disease.
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PMID:Molecular genetics: cardiac disease and risk-related genes. 748 15

The aim of this study was to examine the influence of inhibition on angiotensin converting enzyme (ACE) of myocardial function and perfusion of the rat impaired by diabetes. Spontaneously diabetic rats were treated with the ACE-inhibitor captopril for 4 months. Cardiac performance was analysed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring changes in epicardial fluorescence after injection of a bolus of fluoresceinisothiocyanate-dextrane (3 kDa) as described previously. As compared to untreated diabetic controls, captopril prevented the increase of end diastolic pressure, coronary perfusion pressure and vascular resistance. The intravascular volume was enlarged and the epicardial perfusion rate increased in hearts of diabetic rats treated with captopril as compared to diabetic controls. Treatment of diabetic rats with the ACE-inhibitor captopril (1) increases the number of perfused capillaries, and (2) can partly prevent the development of cardiac dysfunction in diabetes. Together with morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats treated with captopril, our data suggest that ACE-inhibition is cardioprotective in diabetes. These observations are also compatible with the assumption that an accelerated generation of angiotensin II may be involved in the pathophysiological chain of events leading to diabetic cardiopathy.
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PMID:The ACE-inhibitor captopril improves myocardial perfusion in spontaneously diabetic (BB) rats. 748 32

Patients with mild to moderate essential hypertension were treated mainly with an ACE inhibitor (delapril, n = 980) or a Ca antagonist (n = 956) for 12 months, and the incidence of cerebrovascular and cardiovascular events as well as drug-related side effects were compared between the two groups. There were no significant differences between the clinical backgrounds of the two groups. In both groups, the blood pressure was decreased significantly from 1 month of treatment onwards, with the degree of reduction being greater in the Ca antagonist group throughout the study period (p < 0.001). Cerebrovascular or cardiovascular events occurred in 11 out of 980 patients in the delapril group and 18 out of 956 patients in the Ca antagonist group (p = NS). Cerebrovascular disease developed in 5 delapril-treated patients and 11 Ca antagonist-treated patients, and heart disease developed in 5 and 7 patients, respectively (both p = NS). Discontinuation of treatment due to side effects was significantly more common in the delapril group than in the Ca antagonist group (p < 0.001). There was no significant difference in the incidence of cerebrovascular and cardiovascular events between the two groups, and the results suggested that blood pressure reduction per se did not necessarily lead to a parallel decrease in cerebrovascular and cardiovascular complications.
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PMID:A 12-month comparison of ACE inhibitor and CA antagonist therapy in mild to moderate essential hypertension--The GLANT Study. Study Group on Long-term Antihypertensive Therapy. 758 34

The distribution of angiotensin converting enzyme was examined in the rabbit brain by in vitro autoradiography with the specific radiolabelled inhibitor 125I-351A. In the rabbit, the highest concentrations of radioligand binding were found in the choroid plexus, blood vessels, subfornical organ, vascular organ of the lamina terminalis, area postrema and inferior olive. High levels of binding were found throughout the basal ganglia, consistent with the results in all other species studied. In the midbrain the central gray and the superior colliculus displayed high levels of binding. In the medulla oblongata high levels of binding were associated with the nucleus of the solitary tract and dorsal motor nucleus of vagus, consistent with the pattern in other species. There was moderate labelling throughout both the cerebral and cerebellar cortices, which contrasts to the rat but is consistent with the situation in primates. Angiotensin converting enzyme (ACE) is more widely distributed in rabbit brain that in rat, human and Macaca fascicularis, and the results suggest ACE has a very general role in the metabolism of neuropeptides. Inhibitors of converting enzyme are very widely used in the treatment of hypertension and heart disease, and the rabbit should provide a useful model for examining the effects of these drugs in the brain.
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PMID:Localization of angiotensin converting enzyme by in vitro autoradiography in the rabbit brain. 766 70

The effect of the angiotensin I-converting enzyme (ACE) inhibitor benazepril (55 mg/kg orally) on the preservation of cardiac performance in diabetic-hypertensive Dahl S rats was investigated. Diabetes mellitus was produced by streptozotocin. Fasting (4-h) blood glucose levels were 279 +/- 50 mg/dL in diabetic Dahl salt-sensitive v 79 +/- 5 mg/dL in nondiabetic Dahl salt-sensitive rats. Cardiac performance was determined at the end of 8 weeks in an isolated perfused working heart apparatus. Peak left ventricular pressure (LVPmax), left ventricular peak negative dP/dt, and coronary flow were depressed in diabetic Dahl S rats (P < or = .05 v control). These deficits in cardiac function were not observed in diabetic Dahl S rats chronically treated with benazepril. The beneficial effects of benazepril apparently were independent of systolic blood pressure reduction. Although plasma ACE activity was increased in diabetic Dahl S rats, plasma renin activity was reduced. This suggests that the beneficial effects of ACE inhibition may be due to an effect upon the kinin system rather than the renin-angiotensin system. The benazepril-associated preservation of cardiac function in this study suggests that ACE inhibitors may be beneficial in the treatment of diabetic heart disease.
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PMID:Preservation of left ventricular function and coronary flow by angiotensin I-converting enzyme inhibition in the hypertensive-diabetic Dahl rat. 782 56

Impaired left ventricular diastolic function is an indicator of early stages of heart disease. In cardiac failure it is not necessarily associated with impaired systolic function and correlates more closely with clinical symptoms or load tolerance. Pharmacotherapy leading to improved diastolic parameters improves also the clinical condition of cardiac failure. Based on data in the literature, the authors analyze drugs which exert a favourable effect on left ventricular diastolic function: ACE inhibitors, calcium channel blockers, beta adrenergic agonists, phosphodiesterase inhibitors, diuretic and direct vasodilating agents, from the aspect of clinical administration.
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PMID:[Pharmacotherapy of diastolic dysfunction in heart failure]. 821 30

The efficacy of angiotensin converting enzyme inhibitors in the treatment of heart disease is due in part to the accumulation of bradykinin (BK). Since BK can exert its effect by influencing cell proliferation, we chose to study the effect of BK on the growth of A10 vascular smooth muscle cells. Ligand binding studies to determine which BK receptor subtypes are present on A10 cells showed that both B1 and B2 receptors were present in approximately equal numbers. Examination of RNA synthesis demonstrated that BK inhibits uridine incorporation in a dose-dependent manner. This decrease in RNA synthesis was blocked by both B1 and B2 receptor antagonists, as well as by addition of indomethacin, a cyclooxygenase inhibitor. The latter result suggested that prostaglandins mediate the biological actions of BK. Consequently, we examined the direct effect of two prostaglandins, PGE2 and PGI2 (prostacyclin), on A10 cells. PGE2 caused a decrease in RNA synthesis, thus mimicking the effect of BK, while PGI2 did not. Therefore, the inhibition of RNA synthesis in A10 vascular smooth muscle cells by BK requires both B1 and B2 receptor subtypes and this action of BK is apparently mediated by de novo synthesis of prostaglandins.
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PMID:Inhibition of RNA synthesis by bradykinin involves both the B1 and B2 receptor subtypes. 863 19

During the last few years, the use of angiotensin converting enzyme (ACE) inhibitors in the treatment of patients with cardiovascular diseases has been increasing. Captopril is the earliest oral ACE inhibitor and was marketed in 1977. The adverse effect most undesirable with vasodilators, particularly in patients with heart disease, is a reflex tachycardia. The absence of tachycardia with the possibility of binding free radicals is the comparative advantage of angiotensin converting enzyme inhibitors. Because of their positive hemodynamic effect, ACE inhibitors should be used as a supplement in the treatment of patients who need aortocoronary bypass. Their use does not exclude the intravenous administration of vasodilators, and only decreases the required therapeutic concentration of these drugs.
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PMID:[Hemodynamic effects of captopril, an ACE inhibitor, in patients after aortocoronary bypass]. 864 34

Ventricular remodeling is a repair process. It can follow myocardial infarction, mechanical overload (for example, in hypertension or valvular heart disease), and also occurs in inflammation and dilated cardiomyopathy. Remodeling can be an (early) adaptive process followed by a maladaptive (late) phase and involves all cells that are present in the myocardium - the myocyte, the interstitial cells, the vascular endothelium, and the immune cells. Despite the varying etiopathology that these different aspects of heart disease share, a similar sequence of molecular, biochemical and mechanical events that can lead to heart failure, myocyte hypertrophy, extensive extracellular matrix production and fibrosis, even in patients who were previously unaffected by the original disease process (for example, inflammation or infarction). Heart failure can be influenced by treatment of the underlying disease and by modification of the remodeling process, for example, by ACE inhibitors (cardioreparation). In experimental animals it has been clearly demonstrated that ACE inhibitors may even prevent a genetically predetermined left ventricular hypertrophy (cardioprevention).
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PMID:Ventricular remodeling. 868 17


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