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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High blood pressure (BP) is associated with increased risk of vascular disease, including myocardial infarction and stroke. Since drugs that lower BP will reduce the risk of those complications of hypertension that are due to high pressure (strokes due to small-vessel disease, including lacunar infarction and intracerebral hemorrhage due to rupture of microaneurysms, heart failure, and renal failure), it has been assumed that such drugs would also reduce the risk of myocardial infarction due to atherosclerosis. However, in addition to hypertension, many other factors are involved in the atherosclerotic process including blood lipids such as cholesterol, blood platelets, and arterial flow disturbances such as turbulence and vortex formation. Some drugs that lower BP have unwanted effects on blood lipids and arterial flow patterns, which are thought to offset the benefit of BP reduction, whereas other drugs have beneficial effects on such factors. Ames has calculated that the adverse effects of antihypertensive drugs on lipids are enough to completely offset the benefit of treating mild hypertension. We have shown that antihypertensive drugs have different effects on blood velocity, and that these effects are associated with differences in the effects of drugs on arterial flow disturbances at the site of carotid stenosis in man, such that propranolol reduced, and hydralazine increased, the occurrence of abnormal high-velocity flow patterns associated with turbulence and vortex formation. In cholesterol-fed hypertensive rabbits (one-kidney Goldblatt), propranolol was more effective than hydralazine in preventing the occurrence of aortic atherosclerosis, even though hydralazine lowered blood pressure more effectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypertension and atherosclerosis: effects of antihypertensive drugs on arterial flow patterns. 248 Nov 60

The functional significance of alterations in contractile proteins was investigated in the chronically overloaded left ventricle of Goldblatt rats and spontaneously hypertensive rats (SHRs). Congestive cardiac insufficiency occurring in late stages of pressure overload is associated with impaired contractility, as well as significant structural dilatation. Only in the event of extreme dilatation, however, would pumping failure occur in the presence of intact myocardial contractile capability. The transformation toward a slower myocardium is associated with a reduced rate of Ca2+ uptake by the sarcoplasmic reticulum. Transformation influences ventricular and myocardial working capacity to a much lesser extent than do the velocity parameters of contraction. Although a fairly homogeneous VM-3 pattern is typical for ventricles when cardiac failure is experimentally induced, extreme myocardial transformation, as such, does not cause congestive failure. With cardiac insufficiency, left ventricular volume, systolic wall stress, and hydroxyproline concentration are overproportionately increased, as related to VM-3 content, whereas noradrenaline content is decreased. This is consistent with the assumption that myocardial transformation is not necessary for the development of these alterations. Myocardial transformation may be promoted by structural dilatation. Extreme transformation, however, should, in turn, decrease contractility, contributing to cardiac failure. A considerable decrease in contractility indirectly causes depletion of the catecholamine stores. The energy-saving effect of myocardial transformation toward a slower muscle cannot compensate for the unfavorable effects of a substantial degree of ventricular dilatation.
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PMID:Functional significance of contractile proteins in cardiac hypertrophy and failure. 248 26

During a 6 month observation period after operation, typical symptoms of congestive heart failure, such as cyanosis, systemic oedema, ascites and pleural effusion occur in the majority of rats which have a combined arteriovenous shunt (AV-shunt) and renal hypertension (Goldblatt II). In the present study, the left ventricle dilated to twice the size of that of age-matched Wistar controls. Developed wall stress increased significantly due to an augmented ratio of radius to wall thickness. Normalized stress-length (stress-midwall circumference) area and maximum rate of stress development (d sigma/dtmax) indicated decreased myocardial work and power capacity. Although the congestive symptoms can only partially be related to impaired cardiac function, this model may be useful for pathophysiological and pharmacological studies of chronic heart failure.
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PMID:Evaluation of left ventricular function in an experimental model of congestive heart failure due to combined pressure and volume overload. 337 42

Experimental results obtained from studies on Goldblatt rats and spontaneously hypertensive rats as well as theoretical considerations render possible an approximate analysis and evaluation of the relative significance of specific factors at different levels of the heart for the manifestation of cardiac failure under chronic pressure overload. In our experimental models congestive failure was never observed independently of structural dilatation. Thus, as a rule dilatation had already set in before symptoms of heart failure became manifest. However, at moderate dilatation of the ventricle, e.g., at double the end-diastolic volume, the geometrical state per se cannot be the cause of hydropic decompensation whereas extreme dilatation would, in principle, cause cardiac pumping failure even in the absence of any impairment of myocardial "contractility". Generally, a more or less marked impairment of myocardial contractile capability was found, which exceeded the effects due to the altered isoenzyme pattern of myosin. As a rule, a reduction in myocardial "contractility" could be ascertained before a marked degree of dilatation was reached. Diffuse fibrosis impairs the contractile capability of the myocardium and certainly contributes to the manifestation of heart insufficiency; although, as a rule, it should not be the main cause. The adaptive transformation of myocardium towards a slower muscle (isoenzyme pattern of myosin; sarcoplasmatic reticulum) as such does not lead to resting insufficiency, not even under persisting pressure load. Further investigations on processes of excitation-mechanical coupling in the advanced stage of cardiac overload are indicated. The absence of sympathetic support to the heart, e.g., following blockade of beta-adrenergic receptors can, in the advanced stage, elicit a transition from the stage of pre-insufficiency to manifest failure. However, this was only observed when dilatation had already occurred. A network of factors are responsible for cardiac insufficiency due to pressure overloading, whereby the respective significance of each component varies, depending on the experimental model used.
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PMID:Pathophysiological mechanisms in cardiac insufficiency induced by chronic pressure overload--an attempt to analyze specific factors in animal experiment. 379 41

Cardiac muscle physiology, cardiac dynamics and energetics of normotensive and hypertensive rats [Goldblatt II, spontaneously hypertensive rats (SHR)] are analyzed in the light of the question of whether a shift in the isoenzyme pattern of myosin in favour of the isoenzyme VM-3--i.e., transformation towards a slower muscle--is the essential factor for manifestation of cardiac insufficiency under chronic haemodynamic overload. Earlier investigations on chemically skinned myocardial preparations with homogeneous VM-3 and VM-1 patterns revealed that the decrease in unloaded shortening velocity attributable to extreme redistribution of the isoenzyme pattern can amount to approx. 40% whereas isometric tension development at the myofibrillar level is not significantly reduced. Findings from old normotensive and spontaneously hypertensive rates show that even substantial prevalence of VM-3 permits adequate ventricular pumping function. The decrease in the systolic parameters observed in later stages of chronic pressure overload may be attributed primarily to regressive alterations (fibrosis, structural dilatation). Under chronic haemodynamic overload, experimentally imposed isoenzyme redistribution towards a faster myocardium (small thyroxine doses) as well as transformation towards a slower muscle (thyrostatic treatment) affects the time parameters of contraction and oxygen consumption more than left ventricular work capacity. Signs of congestive heart failure are absent. It is concluded that mere transformation of myocardium towards a more slowly functioning muscle should not be considered the cause of cardiac failure in the rat model although this adaptive process may have detrimental consequences under certain conditions.
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PMID:Cardiac alterations at the myofibrillar level: is a redistribution of the myosin isoenzyme pattern decisive for cardiac failure in haemodynamic overload? 624 88

The inotropic responsiveness to adrenergic stimulation is diminished in hypertension associated with left ventricular hypertrophy (LVH). This was shown in hypertrophied hearts from renal hypertensive rats (RHR) (two-kidney, one clip hypertension, Goldblatt) 6 weeks after renal artery clipping when compared to age-matched normotensive sham-operated controls (NR). The isoproterenol-stimulated inotropic responses (delta peak dP/dt) of isolated hearts perfused at constant pressure were significantly lower in RHR than in NR (p less than 0.001 by analysis of variance and covariance, including repeated measures). This reduction in ventricular responsiveness of isolated hearts from RHR did not extend to other inotropic agents such as calcium ions and the cardiotonic cardiac glycoside scillaren. Assay of beta-adrenergic receptors by binding to (-) [3H] dihydroalprenolol showed that left ventricular beta-receptor numbers (fmol per mg membrane protein) were significantly reduced in RHR compared to NR (28.2 +/- 1.1 vs 36 +/- 2.6, p less than 0.01) with no significant change in affinity (Kd,nM) (1.9 +/- 0.27 vs 2.26 +/- 0.34,NS). The results of this study suggest that LVH in renovascular hypertension is associated with impairment in inotropic responsiveness to beta-receptor stimulation parallel with and, in part, related to, a reduction in ventricular beta-receptor concentrations. Such blunting of inotropic responsiveness to beta-adrenergic stimulation may be one of the mechanisms in the progression from LVH to heart failure in hypertensive disease.
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PMID:beta-Receptors and contractile reserve in left ventricular hypertrophy. 629 4

Modifications to cell relaxation and handling of intracellular Ca have been demonstrated in animals with cardiac cell hypertrophy leading to decompensated heart failure. A previously described model of renal hypertension leading to cardiac cell hypertrophy in the guinea pig, produced using the Goldblatt 2-kidney, 1-clip technique, was used to investigate which of the main mechanisms causing cell relaxation (the sarcoplasmic reticulum Ca-adenosinetriphosphatase and Na/Ca exchanger) are altered in hypertrophy. Relaxation upon rewarming from a rapid cooling contracture was slowed in hypertrophied (H) compared with control (C) cells. Relaxation was further slowed in H compared with C cells when Na/Ca exchange was inhibited by rewarming in a Na-free, Ca-free solution and slowed most markedly in H cells in the presence of 10 mM caffeine. Hypertrophy led to greater modification of cell length relaxation in comparison with the decline in the indo-1 transient, but the force-pCa relationship in skinned muscles showed that myofilament sensitivity was unchanged. Such results indicate that cell relaxation and Ca handling are affected in hypertrophy, possibly involving modifications of Na/Ca exchange activity.
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PMID:Effect of hypertrophy on mechanisms of relaxation in isolated cardiac myocytes from guinea pig. 797 15

The endothelins (ET) are potent 21-amino-acid vasoconstrictor peptides produced in many different tissues, particularly in the endothelium of blood vessels. ET-1 is the main endothelin secreted by the endothelium, and acts in a paracrine or autocrine fashion on blood vessels by interacting with ETA or ETB receptors on smooth muscle to stimulate contraction or on ETB receptors on endothelial cells to induce the release of vasorelaxants (nitric oxide and prostacyclin). Production of ET-1 is enhanced in several experimental models of hypertension in the rat, such as sodium-sensitive forms, e.g. deoxycorticosterone acetate (DOCA)-salt hypertensive, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, as well as other models such as stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-K 1C Goldblatt hypertensive rats. In contrast, SHR, 2-K 1C Goldblatt hypertensive rats and nitric oxide-deficient (L-NAME-treated) hypertensive rats do not exhibit an ET-1 component. Endothelin dependency is manifested by excessive vascular growth, particularly in small arteries, and blood pressure lowering and regression of vascular growth after treatment with endothelin antagonists. The latter may be combined ETA/ETB or selective ETA antagonists, of which several are orally active and already in clinical development. In humans, endothelin-dependent vascular tone has been shown in studies of forearm blood flow. Enhanced expression of ET-1 mRNA has been demonstrated in the endothelium of small arteries of patients with moderate to severe hypertension. In a 4-week trial the combined ETA/ETB antagonist bosentan reduced the blood pressure of essential hypertensive patients equally to enalapril. Bosentan improved hemodynamics in patients with heart failure in acute and 2-week-long studies. Endothelin antagonists also offer promise in a rapidly fatal condition, primary pulmonary hypertension. Thus, the endothelin system appears to be involved in different forms of cardiovascular disease in experimental animals and humans, and its interruption offers great promise as a new therapeutic intervention in hypertension, heart failure and other diseases.
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PMID:Endothelin and endothelin antagonists in hypertension. 988 74

The role of endothelins (ET) in blood pressure elevation remains controversial. Data supporting involvement of the ET system in different forms of genetic and experimental hypertension in the rat has appeared in the literature in recent years. Production of endothelin (ET)-1 may be enhanced in several experimental rat models of hypertension. Examples of these exhibiting increased preproendothelin-1 mRNA or peptide in the vasculature include salt-sensitive forms like deoxycorticosterone (DOCA)-salt hypertension, DOCA-salt treated spontaneously hypertensive rat (SHR) and Dahl salt-sensitive rats, and other models like stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-kidney 1 clip (1-K 1C) Goldblatt hypertensive rats. SHR, 2-kidney 1 clip (2-K 1C) Goldblatt hypertensive rats and chronic N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive rats do not appear to exhibit an ET-1 component. Significant vascular growth, and a hypotensive response and regression of vascular growth after treatment with an ET antagonist demonstrate the endothelin-dependency present in some hypertensive models. Severity of high blood pressure elevation, salt-sensitivity and insulin resistance may be common denominators of involvement of the ET system in hypertension. ET antagonism in hypertension may result in regression of vascular damage, prevention of stroke and renal failure and improvement of heart failure. Whether the same is true in human hypertension remains to be established.
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PMID:Endothelin: role in experimental hypertension. 1097 78

Diastolic dysfunction is a major component of hypertensive cardiomyopathy contributing to a progressive evolution towards overt heart failure. To establish an experimental model that could mimic the human clinical pattern, we standardized the surgery in one-kidney, one-clip Goldblatt (1K,1C) rabbits and characterized their hypertensive cardiopathy by echocardiography. Five weeks after placement of a stenotic string around the left renal artery and removal of the right kidney, arterial pressure was measured and an echocardiography performed in conscious animals. An hypertrophic cardiopathy associated with hypertension and a primary trouble of the LV relaxation was observed. This trouble was characterized by a reversion of E/A and Ea/Aa ratios and an increase of the isovolumic relaxation time and Tau index, without augmentation of left ventricular filling pressures. We show for the first time, in this experimental model, a diastolic dysfunction pattern close to the human one. Moreover, echocardiography in a conscious state gives the opportunity to use this model for future chronic pharmacological studies.
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PMID:Echocardiography in conscious 1K,1C Goldblatt rabbits reveals typical features of human hypertensive ventricular diastolic dysfunction. 1804 8


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