Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence has been presented regarding alterations of contractile behavior muscle biochemistry, and ulstrastructure during the course of the hereditary hamster cardiomyopathy. Also, preliminary structural and mechanical data were presented on the acquired cardiomyopathy of diabetes mellitus in experimental animals. In the hamster model, contractile performance, measured as isometric tension and rate of tension development, was shown to be depressed throughout the course of the disease, whereas normalized force-velocity relationships returned to normal only during the compensated stages of hypertrophy. Force-frequency relationships were depressed in myopathic muscles, indicating the presence of alterations in the muscle activation system, namely, the biochemical and functional integrity of the sarcoplasmic reticulum. Analysis of the contractile proteins in myopathic muscle has revealed depressions of Ca2+ activity in purified myosin in addition to an independently increased neutral protease activity that results in the specific degradation of LC2 of myosin. Sympathetic time and norepinephrine turnover increase progressively during the course of the disease. These changes are accompanied by decreasing tissue levels of neorepinephrine and increasing levels of dopamine, indicating a shift in the rate-limiting step for norepinephrine synthesis. Alterations were also noted in nuclear protein composition and serotonin levels. Microscopically, the myolytic and calcification changes that characterize the hamster cardiomyopathy have been confirmed. In addition, contraction bands and lysosomal changes have been observed that may relate to cateholamine hypersensitivity. In the experimental model of diabetic cardiomyopathy, a significant alteration in relaxation process was demonstrated despite the fact that peak tension development and its rate of development were unaltered. Also, the length dependence of contractile behavior was altered when compared to that of age-matched controls, indicating a potential loss of contractility reserve. When animals with combined hypertension and diabetes were studied, bothe contraction and relaxation processes were affected to a greater degree.
 ...
PMID:Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features. 15 9

Left ventricular function was assessed by measuring sytolic time intervals in insulin-requiring diabetics with and without significant microangiopathy. The results were compared with those in normal controls. Significant microangiopathy was defined as proteinuria over 3 g/24 h or proliferative retinopathy. Left ventricular function was also assessed one and a half years later by echocardiography in four patients with microangiopathy. Patients with angina, previous myocardial infarction, hypertension, and alcoholism were excluded. All had normal electrocardiograms and chest radiographs. Diabetics with microangiopathy had impaired left ventricular function, whereas those with uncomplicated diabetes had normal function. This finding supports the existence of a specific diabetic cardiomyopathy due to microangiopathy rather than the metabolic defect. The association of microangiopathy and impaired left ventricular function may explain the high immediate mortality and the high incidence of cardiogenic shock and congestive heart failure after myocardial infarction in diabetics.
 ...
PMID:Diabetic cardiomyopathy: the preclinical phase. 86 81

In diabetic patients, without coronary heart disease and hypertension, left ventricular filing dysfunction exist, that is registered by echocardiography. It is manifested as greater peak flow velocity during atrial systole and as shorter time from the aortic second heart sound to the peak of the early diastolic flow velocity curve. The diastolic dysfunction indicates increased left ventricular stiffness and may be the first maker of diabetic cardiomyopathy.
 ...
PMID:[Subclinical disorders of left ventricular function in diabetics detected by echocardiography]. 130 10

The hypothesis that diabetes mellitus provokes a specific cardiomyopathy is supported by numerous clinical, epidemiological and anatomopathological studies. However, the frequent association of diabetes mellitus with other conditions, such as hypertension and coronary atherosclerosis, both capable of causing the dysfunction of the cardiac muscle, makes it difficult to interpret many of the data reported in the literature and contributes to the continuing debate regarding the effective existence of diabetic cardiomyopathy and its possible pathogenetic mechanisms. In clinical terms, diabetic cardiomyopathy is manifested both as an altered diastolic and/or systolic phase, assessed using various non-invasive techniques, or as congested cardiac decompensation. The pathogenesis of diabetic cardiomyopathy is still not altogether clear. The alteration of the smallest coronary vessels might be responsible for the increased interstitial fibrosis found in the heart of diabetic patients. In this paper numerous data from the literature on this argument are reported and the authors advance the hypothesis that endothelial dysfunction may play a pathogenetic role in the development of cardiopathy.
 ...
PMID:[Diabetic cardiomyopathy: possible pathogenetic role of coronary microcirculation]. 163 Jun 65

Hypertension is known to potentiate the risk of congestive heart failure (CHF) in diabetic individuals. Receptor-effector systems for atrial natriuretic peptide (ANP), which is known to regulate intracellular calcium (Ca2+), were studied in the kidney during hypertensive-diabetic cardiomyopathy in rats. Animals were divided into four groups: control, diabetic (D), hypertensive (H), and diabetic plus hypertensive (D + H). Diabetes was induced by a streptozotocin (65 mg/kg) injection and hypertension was induced by abdominal aortic constriction; studies were done at 1 and 6 weeks. Plasma ANP was increased at 1 week in the D, H, and D + H groups. There was a significant increase in the activity of Ca2+ + magnesium (Mg2+) adenosine triphosphatase (ATPase), which acts as a Ca2+ pump, in the kidney basolateral membrane from D, H, and D + H group at the 1 week study. Ca2+ + Mg2+ ATPase, on the other hand, was significantly decreased in the D + H group only at 6 weeks. This was associated with a decrease in plasma ANP, an increase in the kidney ANP receptor number, and a decrease in guanylate cyclase activity. The response of the Ca2+ pump to ANP was also attenuated. Since ANP is known to mediate its cellular effects in part by increasing Ca2+ + Mg2+ ATPase, the observed changes in the D + H group may contribute to the development of nephropathy and CHF.
 ...
PMID:Congestive heart failure in diabetes with hypertension may be due to uncoupling of the atrial natriuretic peptide receptor-effector system in the kidney basolateral membrane. 164 1

To understand the mechanisms of diabetic cardiomyopathy and the consequences of combined hypertension and diabetes, cardiac tissue responses to various inotropic agents were measured in experimental diabetes. Streptozotocin was injected into Wistar rats, spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Six weeks after the injection diabetic rats showed a subsensitivity to beta adrenergic stimulation in ventricular tissue and a supersensitivity and hyper-responsiveness to Ca++ and alpha adrenergic stimulation (except in WKYs) in ventricular tissues and left atria. A supersensitivity to BAY K 8644 in SHR left atria and a hyper-responsiveness to verapamil in ventricular strips were also noted. These alterations may be due to a change in receptor number or to postreceptor alterations. Diabetic SHRs exhibited greater changes in several of the drug responses (responses to isoproterenol, phenylephrine and BAK 8644) were more hyperlipidemic and had a high mortality as compared with Wistar rats and WKY diabetics. These findings confirm that the combination of hypertension and diabetes results in greater cardiac pathology than is seen with either disease alone.
 ...
PMID:Altered inotropic responses in diabetic cardiomyopathy and hypertensive-diabetic cardiomyopathy. 170 26

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.
 ...
PMID:The future of calcium channel blocker therapy in diabetes mellitus. 172 50

Patients with diabetes mellitus are particularly vulnerable to cardiovascular disease. Although both the macrovascular and microvascular complications are present in patients with diabetes alone, they are particularly severe in patients with both diabetes and hypertension. While there is no doubt that a primary diabetic cardiomyopathy occurs with functional consequences, considerable evidence--both in humans and in experimental animal models--points to hypertension as of critical importance in the pathogenesis of severe pathological and symptomatic diabetic heart disease. In hypertensive-diabetic cardiomyopathy, the histopathologic myocardial damage has been attributed to hypertension, while the myocellular dysfunction has been attributed to diabetes. Together, the consequences to the myocardium are devastating. Strict control of the hypertension and diabetes mellitus, along with prevention of the microvascular consequences of both conditions, may have an ameliorative effect on the subsequent development of diabetic heart disease.
 ...
PMID:The diabetic heart: clinical, experimental and pathological features. 192 63

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar-Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs-Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment. 205

Diabetic cardiomyopathy appears to be due to "premature ageing" of the myocardium which loses some of its compliance and becomes less sensitive to catecholamines. The condition seems to be severe mainly in those frequent cases where it is associated with hypertensive and/or ischaemic cardiomyopathy. Neuropathic denervation of the heart, usually partial and predominantly affecting the parasympathetic system, might play a part in the myocardial dysfunction. It has been held responsible for sudden death, but its real consequences in diabetic patients remain to be assessed. Coronary artery disease is the most common cardiac complication of diabetes mellitus: it accounts for 50 per cent of deaths among noninsulin-dependent, and 25 per cent among insulin-dependent diabetic subjects. Its incidence does not seem to decline and its severity, notably in women, is demonstrated by a mortality rate that is twice as high as that observed in the non-diabetic population; hence the importance of primary prevention and treatment of risk factors. However, the specificity to abnormal lipid metabolism, notably hypertriglyceridaemia, the potentiation by chronic hyperglycaemia of the harmful effects of arterial hypertension, and the possible responsibility of coagulation disorders and hyperinsulinism are points that have not yet been elucidated. We still do not know whether the objectives to be attained in terms of plasma cholesterol, triglycerides and fibrinogen levels, as well as of blood pressure values, should be different in diabetic and non-diabetic subjects. In any case, the treatment of risk factors should be accompanied by a systematic search for silent ischaemia which is 2 to 3 times more frequent among diabetic patients. Detection of silent ischaemia by electrocardiography during exercise and/or Holter recordings, and by echocardiography and/or thallium scintigraphy should be performed not only in diabetic patients with coronary artery disease but also to those with other risk factors or albuminuria.
 ...
PMID:[Heart involvement in diabetic patients]. 213 51


1 2 3 4 5 6 7 8 9 10 Next >>