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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p<0.01) and cell area (p<0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p<0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p<0.05), cell width (p<0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal alpha-actin (p<0.01) and enhanced MLC-2v phosphorylation (p<0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p<0.01), increased cell width (p<0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system.
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PMID:Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats. 1701 64

The present study aimed to investigate the effects of olmesartan, an antagonist for angiotensin II receptor type 1(AT1), on the activation of extracellular signal-regulated kinases (ERK)1/2, tissue remodeling, and pro-inflammatory signals in the right ventricle and lung of mice during the early phase of hypobaric hypoxia. Phosphorylation of ERK1/2 in both tissue types in response to hypoxia peaked at 1-3 days, and declined rapidly in the right ventricle, whereas in the lung it was sustained for at least 8 days. Upregulation of angiotensinogen mRNA was observed in the hypoxic lung at 4-9 days, but not in the hypoxic right ventricle and pulmonary artery. Olmesartan inhibited the hypoxia-induced phosphorylation of ERK1/2 in the lung, but not in the right ventricle. Neither right ventricular hypertrophy nor the thickening of the intrapulmonary arterial wall was ameliorated by olmesartan. However, this drug inhibited the expression of the mRNA for angiotensinogen and several pro-inflammatory factors, including interleukin-6 and inducible nitric oxide synthase in the hypoxic lung. These results suggest that olmesartan blocks a potential positive feedback loop of the angiotensin II-AT1 receptor system, which may lead to attenuate pro-inflammatory signals in the mouse lung, that are associated with hypoxic pulmonary hypertension, without inducing any appreciable effects on the compensatory cardiopulmonary hypertrophy at an early phase of exposure to a hypobaric hypoxic environment.
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PMID:Effects of olmesartan, an AT1 receptor antagonist, on hypoxia-induced activation of ERK1/2 and pro-inflammatory signals in the mouse lung. 1708 97

A crosstransplantation study between genetically matched angiotensin AT1 receptor knockout and wild-type mice revealed that renal AT1 receptors are required for the development of angiotensin II-induced hypertension (). However, in this experimental setting, hypertension-related left ventricular hypertrophy seemed to depend on blood pressure elevation rather than on the expression of AT1 receptors in the heart.
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PMID:Angiotensin in the kidney: a key to understanding hypertension? 1718 2

The physiological role of the renin angiotensin aldosterone system (RAAS) is to maintain the integrity of the cardiovascular system. The effect of angiotensin II is mediated via the angiotensin type I receptor (AT1 ) resulting in vasoconstriction, sodium retention and myocyte growth changes. This causes myocardial remodeling which eventually leads to left ventricular hypertrophy, dilation and dysfunction. Inhibition of the RAAS with angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction has been shown to reduce cardiovascular morbidity and mortality. Angiotensin receptor blockers (ARBs) specifically inhibit the AT1 receptor. It has not been known until the performance of the VALIANT (valsartan in acute myocardial infarction trial) whether blockade of the angiotensin receptor with an ARB or combination of an ACE inhibitor and ARB leads to similar outcomes as an ACE inhibitor. The VALIANT trial demonstrated equal efficacy and non-inferiority of the ARB valsartan 160 mg bid compared with captopril 50 mg tds, when administered to high risk patients with left ventricular dysfunction or heart failure in the immediate post myocardial infarction period. The combination therapy showed no incremental benefit over ACE inhibition or an ARB alone and resulted in increased adverse effects. This review examines the role of valsartan in left ventricular dysfunction post myocardial infarction. We also discuss pharmacokinetics, dosing, side effects, and usage in the elderly.
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PMID:Valsartan in the treatment of heart failure or left ventricular dysfunction after myocardial infarction. 1796 73

It is suggested that angiotensin II is involved in the pathogenesis of pulmonary hypertension and subsequent right ventricular hypertrophy; therefore, an angiotensin AT1 receptor antagonist could be beneficial for the treatment of this disease. We tested the effect of the new AT1 receptor antagonist olmesartan medoxomil on monocrotaline-induced pulmonary hypertension in rats. At 3 weeks after a single subcutaneous injection of monocrotaline (50 mg/kg), the lung/body weight ratio, the right ventricle/(left ventricle plus septum) weight ratio [RV/(LV+S)], and right ventricular systolic pressure were increased, indicating establishment of pulmonary hypertension and right ventricular hypertrophy. Oral administration of olmesartan medoxomil (2 or 5 mg/kg/day for 3 weeks) restored RV/(LV+S) and right ventricular systolic pressure, and a higher dose (5 mg/kg/day) improved the lung/body weight ratio. Pulmonary arteries isolated from monocrotaline-treated rats exhibited an increase in basal tone in the resting state, indicating that they had intrinsic tone. Three weeks of treatment with olmesartan decreased this intrinsic tone. These data suggest that long-term treatment with olmesartan has beneficial effects on monocrotaline-induced pulmonary hypertension and subsequent right ventricular hypertrophy.
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PMID:Evaluation of olmesartan medoxomil in the rat monocrotaline model of pulmonary hypertension. 1820 64

Left ventricular hypertrophy (LVH) and atrial fibrillation (AF) are strong predictors of cardiovascular (CV) morbidity and mortality, independently of blood pressure levels and other modifiable and nonmodifiable risk factors. The actions of circulating and tissue angiotensin II, mediated by AT1 receptors, play an important role in the development of a wide spectrum of cardiovascular alterations, including LVH, atrial enlargement and AF. Growing experimental and clinical evidence suggests that antihypertensive drugs may exert different effects on LVH regression and new onset AF in the setting of arterial hypertension. Since a number of large and adequately designed studies have found angiotensin II receptor blockers (ARBs) to be more effective in reducing LVH than beta-blockers and data are also available showing their effectiveness in preventing new or recurrent AF, it is reasonable to consider this class of drugs among first line therapies in patients with hypertension and LVH (a very high risk phenotype predisposing to AF) and as adjunctive therapy to antiarrhythmic agents in patients undergoing pharmacological or electrical cardioversion of AF.
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PMID:Angiotensin II receptor blockers and cardiovascular protection: focus on left ventricular hypertrophy regression and atrial fibrillation prevention. 1862 60

Left ventricular hypertrophy represents the structural mechanism of adaptation of the left ventricle as the answer of a chronic pressure overload in arterial hypertension. Initially an increment in left ventricular wall thickness occurs. In this stadium of "concentric hypertrophy" LV systolic wall stress, LV ejection fraction and myocardial oxygen consumption per weight unit myocardium remain unchanged. In the further time course of disease LV dilatation will be present. In this phase of "excentric hypertrophy" LV systolic wall stress and myocardial oxygen consumption per weight unit myocardium rise and LV ejection fraction decreases. Patients with arterial hypertension frequently complain of angina pectoris. Angina pectoris and the positive exercise tolerance test or the positive myocardial scintigraphy are the consequence of the impaired coronary flow reserve. The coronary flow reserve is diminished due to structural and functional changes of the coronary circulation. ACE-inhibitors and AT1-receptor blockers cause a significant improvement of coronary flow reserve and regression of both left ventricular hypertrophy and myocardial fibrosis.
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PMID:[Hypertrophy and coronary reserve]. 1908 2

Angiotensin II plays an important role in the cardiovascular continuum starting with risk factors and progressing to atherosclerosis, target organ damage, and ultimately to heart failure, stroke, or death. Inhibiting the renin-angiotensin-aldosterone system (RAAS) represents a cornerstone for the treatment of hypertension and heart failure. In patients with heart failure, the single RAAS blockade with angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce morbidity and mortality, increase life expectancy, and preserve the renal function. AT1 receptor blockers (ARBs) are equally effective in reducing mortality and morbidity in patients with impaired left ventricular function. The combination of ACE inhibitors with ARBs leads to an additive blood pressure lowering effect, better reduction in proteinuria, and to additive benefits in heart failure and left ventricular hypertrophy. But combination therapy is also associated with more side effects. Further investigations evaluating the effect of dual RAAS blockade on fatal and nonfatal cardiovascular events are needed.
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PMID:Dual blockade versus single blockade of the renin-angiotensin system in the light of ONTARGET. 1949 15

Left ventricular hypertrophy (LVH) is considered a major predictor of cardiovascular morbidity and mortality. While it is unanimously accepted that the angiotensin AT1 receptor is involved in the pathogenesis of hypertension and LVH, the role of the AT2 receptor in LVH is still controversial. Most studies addressing the involvement of the AT2 receptor in LVH have been performed in genetically altered, either AT2 receptor-deficient or AT2 receptor-overexpressing mice. Unfortunately, this experimental approach turned out to yield highly controversial results with an almost equal number of studies supporting prohypertrophic or antihypertrophic or neutral effects of the AT2 receptor in LVH. Interestingly, in-vivo studies in wild-type animals using the AT2 receptor antagonist, PD123319, are less controversial and mainly revealed antigrowth effects of the AT2 receptor provided the study duration was sufficiently long. In the future, the novel non-peptide AT2 receptor agonist, compound 21, will allow the effects of the AT2 receptor in LVH to be studied by direct, selective AT2 receptor stimulation in vivo- a novel approach, which will hopefully help to overcome current controversies.
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PMID:The angiotensin AT2 receptor in left ventricular hypertrophy. 2082 17

Losartan, the first AT1 receptor blocker (ARB), was FDA approved 15 years ago. During those years, researchers and clinicians have developed a growing base of knowledge on the benefits of losartan, particularly for hypertension and renal disease. These benefits include decreasing proteinuria, slowing the progression of diabetic nephropathy, controlling hypertension, and decreasing stroke risk in patients with left ventricular hypertrophy. Although many of the benefits of losartan represent a class effect for ARBs, losartan has pharmacokinetic and pharmacodynamic characteristics and effects that are unique and are not a class effect. For example, a shorter duration of action is seen with this first ARB compared with other more recently approved ARBs. Losartan also has a uricosuric effect not seen in other ARBs and attenuates platelet aggregation, which is not seen or is seen to a lesser extent with the other ARBs. This review presents the physiological effects of losartan on the kidney and discusses relevant clinical outcomes.
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PMID:Fifteen years of losartan: what have we learned about losartan that can benefit chronic kidney disease patients? 2169 34


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