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

This study was designed to investigate the role of angiotensin (Ang II) in the cardioprotective effect of ischemic preconditioning. Isolated perfused rat heart was subjected to global ischemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically by using triphenyl tetrazolium chloride (TTC) staining. Four episodes of ischemic/Ang II preconditioning markedly reduced LDH and CK release in the coronary effluent and decreased myocardial infarct size. The cardioprotective effect of Ang II preconditioning was abolished by CV 11974, AT1-receptor antagonist, whereas no such effect was noted with CV 11974 in ischemic preconditioning. PD 123319, AT2-receptor antagonist, produced no marked effect on Ang II preconditioning and ischemic preconditioning induced reduction in myocardial injury. On the basis of these results, it may be concluded that activation of AT1 receptors may be involved in angiotensin-induced pharmacologic preconditioning. But it may not be involved in the cardioprotective effect of ischemic preconditioning in isolated rat heart.
 ...
PMID:Role of angiotensin in cardioprotective effect of ischemic preconditioning. 1022 65

Angiotensin II (AII) acts by 2 types of receptors: the ATI receptor which mediates its actions on vasoconstriction, renin (inhibition) and aldosterone (stimulation) secretions, cellular proliferation and angiogenesis and the non-AT1 (often called AT2) receptors. Mainly expressed in the embryon these latter may favor cellular differentiation and recruitment of collateral circulation. Angiotensin converting enzyme inhibitors (ACEI) decrease the synthesis of All and therefore the stimulation of both receptor types whereas AT1-receptor antagonists (AT1RA) block only the stimulation of these latter and increase the stimulation of AT2 receptor since they increase the production of All secondarily to the inhibition of the feedback of renin secretion by All. Experimentally ACEI and AT1RA decrease angiogenesis and cellular proliferation and favor cellular differentiation which could explain the protective effect of ACEI against cancer suggested recently in a Scotish study. Despite of their common suppressive effect on angiogenesis AT1RA may better than ACEI protect against ischemic events specially the cerebral ones because they favor the rapid recruitment of collateral circulation. This has been demonstrated for losartan in case of abrupt ligation of the carotid in the gerbil since its previous administration protects against fatal cerebral ischemia whereas its previous administration with enalapril abolishes this protection. These data may explain why, in the CAPP trial, captopril which has prevented more effectively diabetes occurrence could not be proved superior to diuretics and/or betablocker in the prevention of myocardial infarction and specially of strokes for which exist on the contrary a suspicion of a lower protection. Therefore a comparative trial between AT1RA and ACEI in the prevention of stroke recurrence should appear as a priority for Public Health and Pharmaceutical Industry Authorities.
 ...
PMID:[Duality of angiotensin II receptors and risk for stroke and cancer: what is the connection?]. 1036 Jan 91

Angiotensin II (AII) participates in regulation of arterial blood pressure through its binding to AII receptors distributing among its target organs. In addition, locally produced AII appears to play a major role in the pathogenesis of cardiovascular hypertrophy via mechanism not related to blood pressure. Two subtypes of AII receptors, AT1 and AT2, are recognized as distinct in both molecular and pharmacological basis. In adult, AT1 is a dominant subtype in cardiovascular system, and mediates virtually all the previously known actions of AII, including vasoconstriction, production of growth factors, hypertrophy of smooth muscle and cardiomyocyte, proliferation of smooth muscle and fibroblast, production of extracellular matrix and so on. Recently, upregulation of AT2 expression is revealed under certain pathological conditions, such as vascular injury, myocardial infarction, and heart failure. Biological significance of AT2 are still under investigation, however, countering actions against AT1 are often suggested.
 ...
PMID:[Distribution and function of angiotensin receptor subtypes in cardiovascular system]. 1036 30

We examined the role of AT1 in the development of cardiovascular remodeling using AT1a knockout (KO) mice. 1. Pressure overload and mechanical stretch induced hypertrophic responses in KO and wild type (WT) cardiomyocytes (CM). Stretch activated MAPK through PKC in WT CM and through tyrosine kinase in KO CM. 2. The number of ventricular premature beats and tachycardia was larger in WT mice than KO mice. 3. Left ventricular remodeling after myocardial infarction was more remarkable in WT mice than KO mice. 4. Vascular injury induced neointimal formation in KO mice as well as in WT mice.
 ...
PMID:[The role of angiotensin II in the development of cardiovascular remodeling]. 1036 40

The renin-angiotensin-aldosterone system has emerged as a potential candidate for the accumulation of collagen in cardiac fibroblasts. The traditional renin-angiotensin-aldosterone system can be considered a system in which circulating angiotensin II or aldosterone is delivered to target tissue or cells. However, an independent local renin-angiotensin system has also been described in cardiac cells and evidence has been accumulated for autocrine and/or paracrine pathways by which biological actions of angiotensin II can be mediated. These actions of angiotensin II are primarily mediated through angiotensin II receptors of the subtype I (AT1). When evaluating the effects of angiotensin II in situ, changes in circulating levels and local production both have to be taken into account. Functional angiotensin II receptors have been documented in cardiac fibroblasts although the presence of aldosterone receptors in cardiac fibroblasts is obscure, and the expression of mRNA for mineralocorticoid receptors in cardiac fibroblasts has been described. In vitro, angiotensin II increased cardiac fibroblast-mediated collagen synthesis and mRNA levels of collagen type I, type III, pro-alpha 1 (I) collagen, pro-alpha 1 (III) collagen and fibronectin, and inhibited matrix metalloproteinase I activity. The ability of angiotensin II to induce collagen synthesis and expression of collagen in cardiac fibroblasts may be mediated by an increase in transforming growth factor-beta 1 in an autocrine/paracrine fashion. The angiotensin II-stimulated secretion and expression of collagen was completely abolished by AT1 receptor antagonism, but not affected by AT2 receptor antagonism. The discordant findings that have been reported concerning the in vitro effect of aldosterone on collagen synthesis in cardiac fibroblasts can at least partly be attributed to differences in methodology such as the use of the total population or a sub-population of cardiac fibroblasts. In vivo, chronic infusion of angiotensin II or aldosterone increased the collagen volume fraction in the ventricles. Angiotensin-converting enzyme (ACE) inhibition and AT1 receptor antagonism, but not AT2 receptor antagonism, reduced collagen deposition in the myocardium in spontaneously hypertensive rats. The cardioprotective mechanism of action of ACE inhibitors can be attributed to local blockade of the formation of angiotensin II, to the degradation of bradykinin or to the release of nitric oxide and/or eicosanoids. Angiotensin-converting enzyme inhibitors also reduced collagen deposition in rat myocardium following myocardial infarction suggesting that collagen deposition may in part result from mechanisms other than through AT1 receptors. However, further research is necessary to unravel the various mechanisms involved in the action of angiotensin-converting enzyme inhibitors or of AT1 receptor antagonists on collagen deposition in the myocardium.
 ...
PMID:Antagonism of the renin-angiotensin-aldosterone system and collagen metabolism in cardiac fibroblasts. 1038 25

Synthesis of aldosterone (Aldo) and corticosterone (B) has been recently reported in rat heart. However, regulation of this synthesis in pathophysiological states remains unknown. Thus, this study aimed to analyze effects of a one-month myocardial infarction (MI) on cardiac steroidogenic system. Levels of terminal enzymes of B (11 beta-hydroxylase: 11 beta H) and aldo (Aldo-synthase: AS) synthesis were assayed by quantitative RT-PCR. Cardiac Aldo and B levels were assessed by celite colum chromatography and radioimmunoassay. MI raised AS mRNA levels by 2.0-fold (p < 0.05) but downregulated that of 11 beta H by 2.4 fold (p < 0.05) in the noninfarcted part of the left ventricle (LV). Cardiac steroids production followed a similar pattern of regulation. Aldo level was increased in MI (319 +/- 85 vs 87 +/- 11 pg/mg of protein in control, p < 0.05) whereas that of B fell (2,412 +/- 318 vs 4,624 +/- 857 pg/mg of protein in control, p < 0.05). MI also induced an 1.9-fold increase in cardiac Ang II level. Such cardiac regulations were prevented by Ang II-AT1 receptor antagonist losartan (8 mg/kg/day) treatment. The Aldo receptor antagonist spironolactone (20 mg/kg/day) had no effect. Plasma Aldo and B, and adrenal 11 beta H and AS mRNA levels were unchanged whatever the treatment. The MI-induced collagen deposition in noninfarcted area of the LV was reduced by both spironolactone and losartan treatments by 1.6- and 2.5-fold, respectively. These data indicate that MI is associated with tissue-specific activation of myocardial aldosterone synthesis. This activation is mediated by cardiac Ang II via AT1 receptor and the resultant increase of intracardiac aldosterone level may be involved in post-MI ventricular remodeling.
 ...
PMID:[Role of cardiac aldosterone in post-infarction ventricular remodeling in rats]. 1048 52

We analyzed the evolution with age of the frequencies of the I/D polymorphism of the angiotensin I-converting enzyme (ACE), a1166c of the angiotensin II AT1 receptor (AT1R), M235T of the angiotensinogen (AGT) and A225V of their methylenetetrahydrofolate reductase (MTHFR) gene in a healthy (H) population and the subsequent comparison to age- and sex-matched groups of myocardial infarction (MI) subjects. A total of 472 H subjects were divided into three groups < 30, 30-55 and > 55 years old and 277 individuals with MI into two groups 30-55 and > 55 years old. The evolution with age showed that the AGT M allele (P < 0.001) and the MTHFR V allele (P < 0.05) frequency decreased with age in H men. The comparison between healthy and MI groups showed that the MM genotype frequency increased in MI men > 55 years (OR =4.16; 95% CI; 1.72-10.1) The cc genotype showed a similar behaviour (OR = 3.96; 95% CI; 1.21-12.9). In men, all the combinations with MM genotype presented a high risk, with OR values between 1.10 and 7.22. In women, the cc genotype increased in the MI > 55 group (OR = 6.66; 95% CI; 2.02-21.9). All the combinations with the cc genotype showed OR values between 1.71 and 13.3. The MM genotype in men and cc genotype in men and women, are independent risk factors for MI. We propose that the study of the allele frequency evolution in an H population at different ages is essential to determine risk factors for MI in case-control studies, since data from isolated age-matched groups can be misinterpreted.
 ...
PMID:The genotype interactions of methylenetetrahydrofolate reductase and renin-angiotensin system genes are associated with myocardial infarction. 1048 56

We investigated whether angiotensin I-converting enzyme inhibition (ACEI) and angiotensin II AT1-receptor blockade (AT1-) would exert beneficial additive effects on coronary hemodynamics and on cardiac remodeling in post-myocardial infarction (MI) heart failure in rats. Wistar rats with MI were treated daily for 6 weeks with either trandolapril (0.1 mg/kg), losartan (3 mg/kg), or their combination, after which coronary hemodynamics (basal and at maximal vasodilation, fluospheres), systemic hemodynamics, and cardiac remodeling were investigated. Neither trandolapril nor losartan (both in nonantihypertensive doses) nor their combination (which significantly decreased blood pressure) proved to be effective at improving MI-induced impairments of basal coronary hemodynamics and of coronary flow reserve, and at preventing cardiac fibrosis development. In contrast, both trandolapril and losartan significantly improved the hemodynamic status [e.g., left ventricular end diastolic pressure: -27% and -39%, urinary cyclic guanosine monophosphate (GMP): -37%, and -26%, respectively] and slightly limited cardiac hypertrophy (-5% and -3%, respectively), and, in their combination, tended to exert additive effects on these three parameters (-49, -42, and -10%, respectively). Thus whereas the ACEI/AT1- combination tended to exert additive effects on systemic hemodynamics and cardiac hypertrophy in post-MI heart failure rats, no such effect was found for coronary hemodynamics, probably in relation to the lack of prevention of cardiac fibrosis. We conclude that an early (6 weeks) drug-induced improvement in coronary hemodynamics does not contribute to the long-term survival prolongation observed in this experimental model after either ACEI or AT1-.
 ...
PMID:Combined selective angiotensin II AT1-receptor blockade and angiotensin I-converting enzyme inhibition on coronary flow reserve in postischemic heart failure in rats. 1059 19

The renin-angiotensin system (RAS) is a widely studied hormonal system that comprises substrate-enzyme interactions, the end result of which is production of the active peptide angiotensin II (Ang II). Because Ang II affects blood pressure control, sodium and water homeostasis, and cardiovascular function and structure, a great deal of research effort has been directed toward blocking the RAS. Angiotensin II may also be involved in end-organ damage in hypertension, heart failure, and vascular disease. At least two subtypes of angiotensin II receptors have been identified: AT1 and AT2. The AT1 mediates all of the known actions of Ang II on blood pressure control. Additionally, research has indicated that the AT1 receptor modulates cardiac contractility and glomerular filtration, and increases renal tubular sodium reabsorption, and cardiac and vascular hypertrophy. Less is known regarding the function of the AT2 receptor. Evidence suggests that the AT2 receptor inhibits cell proliferation and reverses AT1-induced hypertrophy. Indeed, these receptors are thought to exert opposing effects. Angiotensin II AT1 receptor antagonists (AT1RA) inhibit the RAS at the receptor level by specifically blocking the AT1 receptor subtype. These drugs induce a dose-dependent blockade of Ang II effects, resulting in reduced blood pressure, urinary protein, and glomerular sclerosis. It is postulated that AT1RA may provide end-organ protection by blocking Ang II effects via the AT1 receptor, yet leaving the AT2 receptor unopposed. Consequently, these agents may reduce the morbidity and mortality that result from myocardial infarction (MI) and other conditions resulting from structural alterations in the heart, kidney, and vasculature.
 ...
PMID:Angiotensin II receptor blockade and end-organ protection. 1061 95

Angiotensin II AT1 receptor blockade (AT1-) has been shown to prolong survival in post-myocardial infarction (MI) heart failure in rats. In this study, we investigated whether an early AT1-induced improvement in coronary vasodilatation reserve (CVR) might be involved in this beneficial effect. Wistar rats with MI were treated daily and orally for 6 weeks with valsartan, 5 (MI-V5) or 50 mg/kg (MI-V50). MI-controls and sham-operated rats (S-controls) received no treatment. Subsequently, systemic and coronary haemodynamics (at baseline and at maximal vasodilatation, CVR fluospheres) were investigated in the conscious state, and cardiac remodelling (hypertrophy and fibrosis) was assessed. As compared to MI-controls. valsartan (5 mg/kg), had no effect on systemic haemodynamics or myocardial hypertrophy and fibrosis development, gave slightly improved basal left and right ventricular coronary flow and resistance values, but decreased left and right CVR values. Valsartan (50 mg/kg), decreased blood pressure (-11%) and left ventricular end diastolic pressure (-32%), limited the development of cardiac hypertrophy (19%) but not that of fibrosis, slightly improved basal left ventricular flow and resistance values but only the right ventricular CVR value was increased. We conclude that in rats with post-MI. an early AT1-induced improvement in coronary haemodynamics is not responsible for the long-term survival prolongation observed. Furthermore. that cardiac hypertrophy was prevented whereas fibrosis was not, suggests that the latter is a pivotal determinant of CVR.
 ...
PMID:Valsartan and coronary haemodynamics in early post-myocardial infarction in rats. 1062 50


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