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)

Heart failure is an important problem for the growing number of persons afflicted with diabetes. Not only is HF more prevalent than in the non-diabetic population but also it carries a graver prognosis. Diabetic cardiomyopathy adds to the already increased risks for developing HF with hypertension and coronary heart disease, leading to systolic and diastolic dysfunction. As LV function deteriorates, increases in RAS and SNS activation may lead to progressive HF and premature death. The greater prevalence and increased mortality risk in diabetic patients supports the role of aggressive HF diagnosis and management, even in asymptomatic patients. Treatment strategies already established for HF have been shown to be effective in the diabetic population, including ACE inhibitors and beta-blockers. There is evidence that glycemic control is also important in improving clinical outcomes. The adverse effects of beta-blockade on carbohydrate and lipid metabolism and vasoconstriction may be circumvented by the use of carvedilol.
 ...
PMID:Treatment of heart failure in patients with diabetes: clinical update. 1191 48

Diabetes mellitus is responsible for abnormalities in the control of endothelium-dependent vascular reactivity observed on both coronary arteries and coronary microvessels. These abnormalities of coronary artery circulation are associated with structural microcirculatory abnormalities even in subjects with angiographically normal coronary arteries. Both these structural and functional abnormalities might be responsible for an inadequate coronary response to an increased myocardial metabolic demand. These could be a key factor in the progressive myocardial alterations and in the physiopathology of diabetic cardiomyopathy. Their role in the genesis of arterial hypertension in diabetic patients remain to be clarified. The main physiopathological mechanisms of endothelial dysfunction are reviewed.
 ...
PMID:[Vascular endothelium: a target organ for diabetes mellitus]. 1203 2

The diabetic cardiomyopathy is a disease caused by diabetes and is characterised by the presence of diastolic and/or systolic left ventricular dysfunction. Diabetes may produce metabolic alterations, interstitial fibrosis, myocellular hypertrophy, microvascular disease and autonomic dysfunction. It is thought that all of them may cause cardiomyopathy. Other abnormalities that are usually associated with diabetes such as hypertension, coronary artery disease and nephropathy should be excluded before diagnosing diabetic cardiomyopathy. There is no evidence that diabetic cardiomyopathy alone can produce heart failure. However, subclinical ventricular dysfunction has been described in young asymptomatic diabetic patients without other diseases that could affect the cardiac muscle. In these cases we should consider that diabetes is the only cause of the myocardial disease. More studies are needed to know the natural history of diabetic cardiomyopathy.
 ...
PMID:[Diabetic cardiomyopathy: concept, heart function, and pathogenesis]. 1215 93

Diabetes is a serious public health problem. Improvements in the treatment of noncardiac complications from diabetes have resulted in heart disease becoming a leading cause of death in diabetic patients. Several cardiovascular pathological consequences of diabetes such as hypertension affect the heart to varying degrees. However, hyperglycemia, as an independent risk factor, directly causes cardiac damage and leads to diabetic cardiomyopathy. Diabetic cardiomyopathy can occur independent of vascular disease, although the mechanisms are largely unknown. Previous studies have paid little attention to the direct effects of hyperglycemia on cardiac myocytes, and most studies, especially in vitro, have mainly focused on the molecular mechanisms underlying pathogenic alterations in vascular smooth-muscle cells and endothelial cells. Thus, a comprehensive understanding of the mechanisms of diabetic cardiomyopathy is urgently needed to develop approaches for the prevention and treatment of diabetic cardiac complications. This review provides a survey of current understanding of diabetic cardiomyopathy. Current consensus is that hyperglycemia results in the production of reactive oxygen and nitrogen species, which leads to oxidative myocardial injury. Alterations in myocardial structure and function occur in the late stage of diabetes. These chronic alterations are believed to result from acute cardiac responses to suddenly increased glucose levels at the early stage of diabetes. Oxidative stress, induced by reactive oxygen and nitrogen species derived from hyperglycemia, causes abnormal gene expression, altered signal transduction, and the activation of pathways leading to programmed myocardial cell deaths. The resulting myocardial cell loss thus plays a critical role in the development of diabetic cardiomyopathy. Advances in the application of various strategies for targeting the prevention of hyperglycemia-induced oxidative myocardial injury may be fruitful.
 ...
PMID:Oxidative stress and diabetic cardiomyopathy: a brief review. 1221 71

Diabetes mellitus is a strong risk factor for the development of cardiovascular disease, and is associated with a worse prognosis. The incidence of congestive heart failure is higher in diabetic patients, although the reasons for this increased rate are debated (higher incidence and severity of coronary heart disease and arterial hypertension, or a true diabetic cardiomyopathy). The treatment of heart failure in diabetic patients does not differ from that of non-diabetic patients, although recent studies of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers offer interesting new perspectives.
 ...
PMID:[Prevention and treatment of congestive heart failure in diabetic patients]. 1238 94

Although kinins have been associated with the regulation of cardiovascular function in left ventricular hypertrophy (LVH) as a consequence of hypertension, myocardial infarction (MI), and/or diabetic cardiomyopathy, less is known about their receptor regulation under these conditions. We have therefore investigated the bradykinin B1-receptor (B1R) and B2-receptor (B2R) mRNA expression in rat models of MI, LVH and diabetes mellitus (DM). Sprague-Dawley rats (SD) were submitted to permanent ligation of the left descending coronary artery (LAD) to induce a MI, whereas DM was induced by a single injection of streptozotocin (STZ). LVH was induced after thoracic aortic banding (AB). Three weeks after MI, six weeks after STZ injection or six weeks after AB, left ventricular (LV) function was characterized using a Millar-tip catheter. Cardiac B1R- and B2R-mRNA expression were analyzed by specific RNase-protection assays (RPA). LV contractility (dP/dt max) was impaired by 40-48% in rats after induction of MI or DM compared to their controls. However, despite an enormous increase in LV end-diastolic pressure (LEVDP) to 310% after AB, LV contractility did not differ compared to the controls. These hemodynamic changes were accompanied by an up-regulation of cardiac B1R- (MI, 288%; STZ, 215%; AB, 4180%) and B2R-mRNA expression (MI, 122%; STZ, 288%; AB, 96%). Up-regulation of both BK-receptor (BKR) types in early stages of cardiac wound healing induced by ischemia and in chronic stages of cardiac remodeling induced by pressure-overload or by hyperglycemia indicates that kinins play a major role in the complex processes of cardiac tissue injury and repair.
 ...
PMID:Regulation of cardiac bradykinin B1- and B2-receptor mRNA in experimental ischemic, diabetic, and pressure-overload-induced cardiomyopathy. 1248 96

Our aim is to summarize and discuss the recent literature linking diabetes mellitus with heart failure, and to address the issue of the optimal treatment for diabetic patients with heart failure. THE STUDIES LINKING DIABETES MELLITUS (DM) WITH HEART FAILURE (HF) : The prevalence of diabetes mellitus in heart failure populations is close to 20% compared with 4 to 6% in control populations. Epidemiological studies have demonstrated an increased risk of heart failure in diabetics; moreover, in diabetic populations, poor glycemic control has been associated with an increased risk of heart failure. Various mechanisms may link diabetes mellitus to heart failure: firstly, associated comorbidities such as hypertension may play a role; secondly, diabetes accelerates the development of coronary atherosclerosis; thirdly, experimental and clinical studies support the existence of a specific diabetic cardiomyopathy related to microangiopathy, metabolic factors or myocardial fibrosis. Subgroup analyses of randomized trials demonstrate that diabetes is also an important prognostic factor in heart failure. In addition, it has been suggested that the deleterious impact of diabetes may be especially marked in patients with ischemic cardiomyopathy. TREATMENT OF HEART FAILURE IN DIABETIC PATIENTS : The knowledge of the diabetic status may help to define the optimal therapeutic strategy for heart failure patients. Cornerstone treatments such as ACE inhibitors or beta-blockers appear to be uniformly beneficial in diabetic and non diabetic populations. However, in ischemic cardiomyopathy, the choice of the revascularization technique may differ according to diabetic status. Finally, clinical studies are needed to determine whether improved metabolic control might favorably influence the outcome of diabetic heart failure patients.
 ...
PMID:Influence of diabetes mellitus on heart failure risk and outcome. 1255 46

Enhanced tissue angiotensin (Ang) II levels have been reported in diabetes and might lead to cardiac dysfunction through oxidative stress. This study examined the effect of blocking the Ang II type 1 (AT1) receptor on high glucose-induced cardiac contractile dysfunction. Rat ventricular myocytes were maintained in normal- (NG, 5.5 mmol/L) or high- (HG, 25.5 mmol/L) glucose medium for 24 hours. Mechanical and intracellular Ca2+ properties were assessed as peak shortening (PS), time to PS (TPS), time to 90% relengthening (TR90), maximal velocity of shortening/relengthening (+/-dL/dt), and intracellular Ca2+ decay (tau). HG myocytes exhibited normal PS; decreased +/-dL/dt; and prolonged TPS, TR90, and tau. Interestingly, the HG-induced abnormalities were prevented with the AT1 blocker L-158,809 (10 to 1000 nmol/L) but not the Janus kinase-2 (JAK2) inhibitor AG-490 (10 to 100 micromol/L). The only effect of AT1 blockade on NG myocytes was enhanced PS at 1000 nmol/L. AT1 antagonist-elicited cardiac protection against HG was nullified by the NADPH oxidase activator sodium dodecyl sulfate (80 micromol/L) and mimicked by the NADPH oxidase inhibitors diphenyleneiodonium (10 micromol/L) or apocynin (100 micromol/L). Western blot analysis confirmed that the protein abundance of NADPH oxidase subunit p47phox and the AT1 but not the AT2 receptor was enhanced in HG myocytes. In addition, the HG-induced increase of p47phox was prevented by L-158,809. Enhanced reactive oxygen species production observed in HG myocytes was prevented by AT1 blockade or NADPH oxidase inhibition. Collectively, our data suggest that local Ang II, acting via AT1 receptor-mediated NADPH oxidase activation, is involved in hyperglycemia-induced cardiomyocyte dysfunction, which might play a role in diabetic cardiomyopathy.
Hypertension 2003 Aug
PMID:AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes: role of the AT1 receptor and NADPH oxidase. 1284 13

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of beta-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. beta-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with beta-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation beta-blocker. Prophylactic utilization of ACE inhibitors and beta-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.
 ...
PMID:Heart failure: the frequent, forgotten, and often fatal complication of diabetes. 1288 75

Diabetic cardiomyopathy is an ill-defined entity. This study was designed to explore the possible association between left ventricular diastolic dysfunction (LVDD) and cardiac autonomic neuropathy (CAN) independently from metabolic control. Three groups of 10 age-matched men each with well-controlled type 2 diabetes were studied: (1) subjects with normal diastolic function, (2) subjects with LVDD characterized by impaired LV relaxation, and (3) subjects with a more severe form of LVDD characterized by a pseudonormalized pattern of LV filling. No subject had evidence of clinical diabetic complications, coronary artery disease (CAD), hypertension, congestive heart failure, or thyroid or overt renal disease, and all had a negative maximal exercise test. LVDD was evaluated by Doppler echocardiographic and CAN was evaluated using spectral analysis of heart rate variability (HRV; time and frequency domains) from 24-hour Holter recordings. Findings showed that the high frequency power (HF: 0.15 to 0.4 Hz) tends to decrease with worsening diastolic function; 5.0 +/- 0.2 ms(2) (mean +/- SE) in group 1, 4.2 +/- 0.3 ms(2) in group 2, and 3.9 +/- 0.4 ms(2) (P =.03) in group 3, respectively, whereas the low frequency power (LF: 0.04 to 0.15 Hz) was similar between groups. In the time domain, the mean squared differences of the successive RR intervals (rMSDD) also showed the same pattern, ie, 31.0 +/- 2.8 ms, 23.8 +/- 1.6 ms, and 21.5 +/- 2.9 ms in groups 1, 2, and 3, respectively (P =.03). The E/A ratio correlated significantly with indices of parasympathetic modulation (HF; r = 0.448, P =.013; rMSDD: r = 0.457, P =.011; pNN50: r = 0.425, P =.019). LVDD and CAN are associated in patients with otherwise uncomplicated well-controlled type 2 diabetes. The parameters defining these 2 abnormalities may serve to better define diabetic cardiomyopathy as a distinct entity and could eventually become useful prognostic indicators as it has been shown in nondiabetic populations.
 ...
PMID:Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes. 1289 73


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