Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Dahl Iwai salt-sensitive (DS) rats have been reported as becoming hypertensive with left ventricular hypertrophy (LVH) and heart failure when on a high-salt diet. Their circulating renin-angiotensin system (RAS) has been reported to be suppressed. To evaluate the role of angiotensin II (AngII) type 1 and type 2 receptors (AT1 and AT2, respectively) in LVH, we compared cardiac AT1 and AT2 receptors in 10-week-old DS rats and Dahl Iwai salt-resistant (DR) rats. 2. Seven pairs of 6-week-old male DS and DR rats were fed either a low- or high-salt diet (0.3 or 8% NaCl, respectively) for 4 weeks. Left ventricular AngII receptors were measured by radioligand binding assays using [125I]-[Sar1,Ile8]-AngII in plasma membrane fractions from these four groups. The AT1 and AT2 receptors were distinguished using their specific antagonists CV 11974 and PD 123319, respectively. 3. The high-salt diet increased blood pressure and the left ventricle:bodyweight ratio in DS rats. However, neither Bmax for AT1 and AT2 receptors nor Kd for [125I]-[Sar1,Ile8]-AngII differed between the groups. These results are different from those of other reports of pressure-overload LVH, such as spontaneously hypertensive rats or renovascular hypertension rats, in which AT1 and AT2 receptors were reported to be up-regulated.
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PMID:Angiotensin II receptors in cardiac left ventricles of Dahl rats. 959 May 78

We studied the effects of chronic blockade of the renin-angiotensin system on hypertension and cardiac left ventricular hypertrophy (LVH) in Dahl salt-sensitive (DS) rats given a high-salt or low-salt diet. [Experiment 1] Twelve-week-old male DS rats were fed an 8% NaCl diet and received the angiotensin II receptor (AT1) antagonist, candesartan (3 mg/kg/d), the angiotensin converting enzyme inhibitor enalapril (30 mg/kg/d), or vehicle for 6 wk after 3 wk of 8% salt-loading. Neither candesartan nor enalapril with concomitant high salt-loading attenuated the blood pressure (BP) elevation. LVH was also not attenuated significantly by these treatments. [Experiment 2] After 8 wk of 8% salt-loading, the rats were given a 0.3% NaCl diet and concurrently received candesartan, enalapril, or vehicle for 5 wk. Switching from the high-salt to low-salt diet significantly decreased BP and left ventricular mass in the vehicle-treated animals. Both candesartan and enalapril normalized BP during salt-depletion; the blockade of the renin-angiotensin system produced an additive reduction in LVH. These findings suggest that sodium intake and hemodynamic load, but not the renin-angiotensin system, may be major determinants of the development of LVH in DS rats.
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PMID:Effects of renin-angiotensin system blockade and dietary salt intake on left ventricular hypertrophy in Dahl salt-sensitive rats. 978 99

The development of left ventricular hypertrophy (LVH) in subjects with hypertrophic cardiomyopathy (HCM) is variable, suggesting a role for modifying factors such as angiotensin II. We investigated whether the angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism, the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and/or plasma renin influence LVH in HCM. Left ventricular mass index (LVMI) and interventricular septal thickness were determined by 2-dimensional echocardiography in 104 genetically independent subjects with HCM. Extent of hypertrophy was quantified by a point score (Wigle score). Plasma prorenin, renin, and ACE were measured by immunoradiometric or fluorometric assays, and ACE and AT1-R genotyping were performed by polymerase chain reactions. The ACE D allele did not affect any of the measured parameters except plasma ACE (P<0.04). LVMI was higher (P<0.05) in patients carrying the AT1-R C allele (190+/-8.3 g/m2) than in AA homozygotes (168+/-7.2 g/m2), and similar patterns were observed for interventricular septal thickness (23.0+/-0.7 versus 21. 6+/-0.7 mm) and Wigle score (7.0+/-0.3 versus 6.3+/-0.3). Plasma renin was higher (P=0.05) in carriers of the C allele than in AA homozygotes. Multivariate regression analysis, however, revealed no independent role for renin in the prediction of LVMI. Plasma prorenin and ACE were not affected by the AT1-R A/C1166 polymorphism, nor did the ACE and AT1-R polymorphisms interact with regard to any of the measured parameters. We conclude that the AT1-R C1166 allele modulates the phenotypic expression of hypertrophy in HCM, independently of plasma renin and the ACE I/D polymorphism.
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PMID:AT1 receptor A/C1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy. 982 39

Cardiac hypertrophy can be caused in different ways, and the effect of hypertrophy on prognosis depends on whether it is concentric or eccentric in nature. It is simplistic to ascribe hypertrophy purely to workload, and it is a complex interaction between workload, wall stress, and the local and humoral environment. In rats, acute elevation of BP occurring during the rats' sleep cycle causes cardiac hypertrophy, and reduction of BP in hypertensive rats during the sleep cycle causes reversal of left ventricular hypertrophy. This may be due to secretion of growth hormone and renin during sleep. Experimental evidence indicates that angiotensin II possibly formed and acting locally may be implicated in the genesis of cardiac hypertrophy; however, angiotensin II by itself causes relatively minor hypertrophy, but this becomes intensified if there is a high sodium intake and a high angiotensin II level. Blockade of the angiotensin system with angiotensin-converting enzyme inhibitors causes reversal of cardiac hypertrophy and similar results are achieved with AT1 receptor blocking drugs, suggesting that bradykinin may be of relatively minor importance. Clinically, the AT1 receptor blocking drugs have few side effects and appear to have similar beneficial effects to angiotensin-converting enzyme inhibitors, making them suitable to treat many people with hypertension.
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PMID:Angiotensin blocking drugs and the heart beyond 2000. 989 72

The renin-angiotensin system (RAS) plays an important role in blood pressure control and in water and salt homeostasis. It is involved in the pathophysiology of hypertension and structural alterations of the vasculature, kidney, and heart, including neointima formation, nephrosclerosis, postinfarction remodeling, and cardiac left ventricular hypertrophy (LVH). Recently, an increased knowledge of the effector peptides of the RAS, their receptors, and their respective functions has led to a new principle of treatment for hypertension: the inhibition of angiotensin (Ang) II via angiotensin-converting enzyme inhibitors or Ang II-receptor antagonists. In this review, the Ang receptors AT1 and AT2 and the potential roles of shorter angiotensin fragments, including Ang III(2-8), Ang IV(3-8), and Ang(1-7), are discussed.
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PMID:The renin-angiotensin system and its receptors. 1002 50

Left ventricular hypertrophy (LVH) represents an independent risk factor for cardiovascular morbidity and mortality, and normalization of left ventricular mass has become a desirable goal of antihypertensive treatment. In a randomized, double-blind study, the angiotensin II (AT1-receptor) antagonist valsartan (Diovan ; 80-160 mg q.d.) was compared with the beta-blocker atenolol (50-100 mg q.d.) over 8 months in previously untreated patients with essential hypertension and LVH. Sixty-nine patients were randomized, of whom 58 were evaluated by echocardiography. After 8 months of treatment in the atenolol group [n = 8 with additional hydrochlorothiazide (HCTZ)], initial blood pressure was reduced from 160/103 to 147/92 mm Hg (p < 0.0001). In the valsartan group (n = 9 with HCTZ), blood pressure decreased from 163/101 to 146/90 mm Hg (p < 0.0001). Left ventricular mass index decreased from 127 to 117 g/m2 in the atenolol group and from 127 to 106 g/m2 in the valsartan group. Long-term treatment with valsartan resulted in a significant reduction of LVH in patients with essential hypertension.
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PMID:Angiotensin II antagonism and the heart: valsartan in left ventricular hypertrophy. 1002 52

At the present time we cannot assume that the proven benefits of ACEI on renal disease will be reproduced by using AT1-ra. With potentially differing modes of activity of these drugs, they cannot be seen as interchangeable and ACEI should remain the drug of choice in patients with progressive renal disease unless they are not tolerated. It is possible that AT1-ra may offer additional advantages in some patients or that synergy exists between the two agents, but this view will remain entirely speculative unless proper trials are conducted. Despite the results of the ELITE study [22], the uncertainty regarding the use AT1-ra in cardiovascular disease mirrors that of renal disease. This issue is obviously of relevance to the nephrologist in view of the spectrum of cardiac disease that accompanies chronic renal failure, such as left ventricular hypertrophy and cardiac failure, which provide multiple indications for manipulation of RAS. Despite their renoprotective effect, previous studies on ACEI [3,4] have not shown an overall reduction in mortality and this issue needs to be addressed in addition to renoprotection in studies comparing AT1-ra and ACEI.
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PMID:Angiotensin converting enzyme inhibitors and angiotensin receptor (AT1) antagonists: either or both for primary renal disease? 1005 68

To evaluate the role of angiotensin II (AII) on diastolic function during post-myocardial infarction (MI) ventricular remodeling, coronary ligation or sham operation was performed in male Sprague-Dawley rats. Experimental animals were maintained on either irbesartan, a selective AT1-receptor antagonist, or no treatment. Measurement of cardiac hypertrophy, diastolic function, and sarcoendoplasmic reticulum adenosine triphosphatase (ATPase; SERCA) and phospholamban (PLB) gene expression was assessed at 6 weeks after MI. Myocardial infarction caused a significant increase in myocardial mass and left ventricular (LV) filling pressure, whereas LV systolic pressure and +dP/dt were reduced. The time constant of isovolumic relaxation (tau) was markedly prolonged after MI. Post-MI hypertrophy was associated with substantial increases in the messenger RNA (mRNA) expression of atrial natriuretic peptide (ANP), but no significant changes in SERCA or PLB levels. Although irbesartan treatment did not significantly alter post-MI LV systolic or filling pressures, it nevertheless effectively decreased ventricular hypertrophy, improved tau, and normalized ANP expression. These results demonstrate that AT1-receptor antagonism has important effects on myocardial hypertrophy and ANP gene expression, which are independent of ventricular loading conditions. In addition, the improvement in diastolic function was not related to changes in SERCA and PLB gene expression, suggesting that enhanced myocardial relaxation was related to the blockade of AII effects on myocyte function or through a reduction of ventricular hypertrophy itself or both.
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PMID:Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular hypertrophy and improves diastolic function in the remodeling post-myocardial infarction ventricle. 1006 80

The 1996 World Health Organization (WHO) recommendations for mild hypertension stressed the need to evaluate target-organ lesions as treatment criteria. The effects of both vascular and heart remodelling on hypertension must to be taken into account, as they adversely influence the prognosis of patients with hypertension. It was previously demonstrated that at least three classes of antihypertensive agents were able to decrease morbidity and mortality in patients with hypertension. Meta-analyses have shown that angiotensin-converting enzyme inhibitors seem to have a marked effect on regression of left ventricular hypertrophy (LVH). However, the relationship between drug-induced LVH regression and reduced morbidity and mortality remains to be confirmed. The effect of antihypertensive agents on vascular hypertrophy, as assessed by intima-media thickness, and their involvement in reducing morbid events, also have to be determined at the vascular level. As experimental data have highlighted the involvement of angiotensin II in animal models of LVH and vascular hypertrophy development, the role of angiotensin II AT1 receptor blockers should also be assessed in this indication.
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PMID:Cardiac and vascular remodelling: effect of antihypertensive agents. 1007 19

We studied the interaction of the central renin-angiotensin system (RAS) and vasopressin system in rats with left ventricular hypertrophy (LVH) due to aortic banding. In these animals plasma vasopressin is elevated and vasopressin content is increased in specific brain areas. Chronic blockade of the RAS by angiotensin-converting enzyme (ACE) inhibition (ramipril) and AT1 receptor antagonism (losartan) significantly attenuated circulating and central vasopressin in rats with LVH. Given the antidiuretic, vasoconstrictive, and growth-promoting effects, vasopressin may participate in the cardiovascular alterations in LVH. Blockade of the RAS strongly ameliorates central and peripheral-vasopressin. Therefore, central modulatory effects on vasopressin might contribute to the therapeutic efficacy of ACE inhibitors and AT1 antagonists.
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PMID:Central vasopressin is modulated by chronic blockade of the renin-angiotensin system in experimental left ventricular hypertrophy. 1019 35


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