Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Family and population studies have reported that blood pressure has a heritability of 30-50%, but simple genetic models do not readily explain the patterns of inheritance of hypertension. 2. Restriction fragment length polymorphisms were used to study allele frequencies of a selection of candidate genes that may be important in determining the genetic component of hypertension. These included the genes for renin, haptoglobin, neuropeptide Y and cardiac myosin beta heavy chain. 3. There was no significant association between alleles at any of these loci and the presence of hypertension in this population, suggesting that the contribution of variation at these loci to the genetic component of the variance in hypertension may be quite small.
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PMID:Polymorphisms of candidate genes in essential hypertension. 135 2

Myocardial pump deficiency is regarded to be the hemodynamic hallmark of congestive heart failure. A decline of arterial pressure in the systemic circulation is counter-regulated by vasoconstriction in the arteriolar vascular bed; the compensatory vasoconstriction, however, results in an increased afterload that in turn aggravates myocardial pump deficiency. As part of the counterregulatory systems the sympathetic nervous system is activated (increase of neuronal activity, increased plasma norepinephrine) and the renin-angiotensin-aldosterone system is stimulated as well (increased plasma renin activity, elevated angiotensin II serum levels, hyperaldosteronism). In parallel, serum levels of antidiuretic hormone (ADH) is despite a serum hypoosmolarity increased and only poorly compensated by release of the atrial natriuretic peptide. On the cellular level, congestive heart failure leads to a shift of the expression of contractile proteins towards to fetal forms (for instance myosin-isoenzymes). Although the counterregulatory activation of the neuroendocrine systems vasoconstricts the peripheral arteries thereby maintaining perfusion of vital organs, the rise in afterload ultimately leads to a progression of congestive heart failure. Consequently, vasodilators (such as ACE-inhibitors) that not only induce vasodilation in the peripheral arteries, but also inhibit progressive neuroendocrine stimulation evolved as excellent compounds for treating congestive heart failure.
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PMID:[Pathophysiology of left heart failure with reference to hemodynamic and neurohumoral changes]. 135 6

In recent years, captopril has attracted considerable clinical attention as an agent for use in treating heart failure. We administered 15 mg/kg of captopril or 1.5 mg/kg of enalapril to 5-week-old J-2-N cardiomyopathic hamsters for 10 or 15 weeks, and investigated the roles of the renin-angiotensin-aldosterone and kallikrein-kinin systems in the onset and progress of cardiomyopathy. In the untreated group, serum creatine kinase levels increased in accordance with the progression of cardiomyopathy, but this increase was markedly inhibited by the administration of captopril. The rise in serum aldolase levels was similarly inhibited. Serum malondialdehyde levels were significantly reduced by the administration of captopril. ECG findings and the ventricular myosin isoenzyme pattern were also markedly improved by captopril. The improvement in all these parameters was less with enalapril. These differences between captopril and enalapril suggest that increases in tissue bradykinin and vasodilatory prostaglandins may play an important role in the beneficial effects of captopril.
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PMID:The effects of angiotensin converting enzyme inhibitors and the role of the renin-angiotensin-aldosterone system in J-2-N cardiomyopathic hamsters. 153 90

Experimental myocardial infarction is a model of cardiac overload due to amputation of part of the cardiac muscle. The development of cardiac failure depends on the size of the infarct and the time factor. This model of overload is associated with changes of the phenotype of the remaining healthy muscle and with peripheral vascular modifications partially dependent of the activation of pressor and/or deactivation of dilator systems. These changes are proportional to the size of the infarction at a given time after induction of the model. The degree of right ventricular hypertrophy and the decrease in blood pressure reflect the severity of infarction and the deterioration of the remaining myocardial function, affecting the haemodynamics both before and after the left ventricle. The increases in the 1/3 forms of isomyosins, the amount of subendocardial collagen, the biosynthesis, stocking and secretion of ANF are related to the infarct size and degree of overload. Similarly, the concentration of cyclic GMP is proportional to the infarct size. These parameters reflect ventricular overload, the increase of stress and energy deprivation of the remaining healthy muscle. The activation of peripheral pressor systems is also dependent on the infarct size reflects the effect of cardiac pump dysfunction on the kidney, liver, brain and endothelium. Large infarcts are associated with increased circulating renin and renal concentrations, with a decrease in angiotensinogen levels related to its consumption by the renin and to reduced hepatic synthesis and also with increased secretion and biosynthesis of vasopressin by the hypothalamus. In this model, Perindopril is beneficial by decreasing the cardiac load. It reduces the blood pressure, causes regression of bi-auricular and right ventricular hypertrophy. Changes in myosin isoenzyme configuration regress and subendocardial fibrosis and ANF concentrations are normalised. The effects of ACE inhibitors in this context, though very beneficial, are limited by the impossibility of normalising cardiac load and stress when the initial amputation of cardiac contractile mass exceeds 40%.
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PMID:[Experimental myocardial infarction in the rat. Effect of perindopril]. 166 27

The morphological features of the juxtaglomerular part of the afferent arteriole presented here are in favor of a bulk fluid flow through the fenestrated endothelium and the urinary space of the glomerulus towards the renin-granulated epithelioid cells and the extraglomerular mesangium. In addition there should be some fluid movement from the glomerular mesangium draining via the glomerular stalk. These flows can be important codeterminants of the interstitial fluid composition around the granular cells and act themselves as a signal to granular or extraglomerular mesangial cells to trigger renin secretion and/or a short-loop (vasculo-vascular) feedback mechanism in governing the glomerular filtration. These studies also provide evidence that the terminal part of the afferent arteriole, consisting of granular cells, lacks the immunoreactive myosin. The role of this vessel segment not only as a putative effector of the tubuloglomerular feedback mechanism, but also as an intrarenal vascular receptor, should therefore be reconsidered. The electrophysiological data presented herein suggest an intrarenal extravascular conversion of Ang I to Ang II in the vicinity of the granular cell. This de novo locally-formed angiotensin II may directly influence the renin secretion, mesangial cell function, and thus tubuloglomerular feedback mechanism and glomerular hemodynamics.
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PMID:Morphology and function of the distal part of the afferent arteriole. 225 66

The inhibition of the renin-angiotensin system (RAS) has important effects on different parameters of left ventricular function. Chronic inhibition of the RAS avoids hypokalemia and potassium losses by increasing aldosterone release. This potassium-sparing effect is likely to prevent cardiac arrhythmia. Inhibition of the RAS reverses cardiac hypertrophy in renovascular and in spontaneously hypertensive rats (SHR), but not in DOCA salt hypertensive rats. Inhibition of the RAS also reverses the decrease in myocardial contractility, as demonstrated by the reversion of isoenzyme profile of cardiac myosin in renovascular hypertensive rats. In DOCA salt hypertensive rats, RAS inhibition has no effect on blood pressure or on cardiac contractility. Despite its peripheral vasodilatory property, inhibition of the RAS does not increase heart rate in relation to a direct negative chronotropic effect of angiotensin II inhibition and to the absence of activation of the baroreflex system. When RAS is activated, its inhibition has a coronary vasodilatory effect, but this coronary vasodilation is associated with a decrease in perfusion pressure and with an increase in intrinsic cardiac contractility. These concomitant effects lead us to conclude that inhibition of RAS probably has no important beneficial effect on the oxygen demand/oxygen supply ratio in the myocardium distal to the coronary artery stenosis.
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PMID:Can inhibition of the renin-angiotensin system have a cardioprotective effect? 240 75

The present study evaluates cardiac function, plasma renin activity (PRA) and left ventricular (LV) myosin isoenzymes in untreated two-kidney, one-clip Goldblatt hypertensive rats (2KIC) and in 2KIC treated with felodipine and metoprolol. Normotensive rats (NCR) and another group of 2KIC, in which the renal artery constriction was removed (UC-2KIC), were also investigated. Cardiac performance was assessed by means of a working heart perfusion device, allowing also for measurements of myocardial oxygen consumption. Following antihypertensive therapy and unclipping, blood pressure became close to normotensive levels. PRA remained equally elevated in treated and untreated 2KIC, but became practically normalized after unclipping. Relative LV weight in 2KIC increased 74% above that in NCR but in treated 2KIC increased by only 20%. In UC-2KIC LV hypertrophy became reversed, LV weight/body being about the same as in treated 2KIC. In treated 2KIC, coronary resistance at maximal dilatation was significantly reduced, implying prevention of hypertensive, structural coronary vascular changes, and optimal LV function was improved markedly in the lower range of perfusion pressures compared with untreated 2KIC. When, however, the hearts were challenged at a high pumping resistance (perfusion pressure), LV function was similar in untreated and treated 2KIC. Myocardial oxygen consumption for given levels of stroke work was significantly lower in treated than in untreated 2KIC. The myosin isoenzyme pattern in the LV of 2KIC was shifted, with significantly higher amounts of VM-3 than in NCR. This shift was normalized by antihypertensive therapy or by unclipping. In conclusion, antihypertensive therapy with felodipine and metoprolol prevents the development of coronary vascular and left ventricular hypertrophy in 2KIC. This may contribute to enhance cardiac performance at low aortic pressure. The lack of improvement in optimal cardiac performance (at high aortic pressure) implies that the hypertensive state per se, rather than extent of pressure elevation, cardiac hypertrophy, or changes of LV isoenzymes, determines the reduced cardiac function in renal hypertensive rats (Friberg & Nordborg 1986).
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PMID:Functional and biochemical analyses of isolated rat hearts in renal and reversed renal hypertension. 252 66

Recent studies have shown that autoreactive B cells and autoantibodies are present in pathological as well as in normal situations. In the present study, we immortalized human B cell lines from normal individuals and from patients with malignant or benign dysglobulinemia with Epstein-Barr virus and examined, after cloning, the autoantibody reactivities of the immunoglobulins secreted by these cells. Forty-two supernatants were analyzed by enzyme-immunoassay on a panel of 13 self and non-self antigens: trinitrobenzenesulfonic acid (TNP), DNA, L-glutamine, L-alanine, L-tyrosine (GAT), actin, myosin, tubulin, albumin, renin, spectrin, transferrin, thyroglobulin, myoglobin, peroxidase, and by immunofluorescence in tissue sections. Fourteen (33%) of the immunoglobulin-secreting cell lines were found to have an autoantibody function; seven secreted IgM, six IgA, and one IgG. The light chains were of the kappa type in 11 cases. The vast majority of these clones reacted with more than five antigens of the panel and all of them reacted with TNP. No correlation was found between a given isotype and an antibody specificity. More than half of these antibodies also reacted with cellular antigens present in tissue sections. None of the four cell lines secreting monoclonal antiviral antibodies reacted with any of the antigens of the panel. The results indicate that immunoglobulins secreted by human monoclonal lymphoid cell lines can have polyspecific autoantibody functions, similar to those found in normal human polyclonal antibodies, in human monoclonal paraproteins and in natural monoclonal antibodies synthesized by murine or rat clones obtained from physiologically normal animals.
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PMID:Polyspecific natural antibodies and autoantibodies secreted by human lymphocytes immortalized with Epstein-Barr virus. 283 Sep 25

The effects of converting enzyme inhibition on the cardiac mass, isomyosins polymorphism, and collagen network in the left ventricle have been studied in renovascular, hypertensive, spontaneously hypertensive, and normotensive rats. The isoenzyme profile of left ventricular myosins was used as an indirect marker of the intrinsic property of contractility, whereas the collagen network, measured by a morphometric method, represented an indirect structural marker of the arrhythmogenic risk. One-clip, two-kidney renovascular hypertension was associated with cardiac hypertrophy, a shift in the isomyosin profile, and accumulation of collagen within the left ventricular myocardium. In this renin-angiotensin-dependent model, one month of treatment with converting enzyme inhibitor normalized blood pressure and consistently reversed cardiac hypertrophy and the isomyosin profile. Converting enzyme inhibitor treatment of 12-week-old spontaneously hypertensive rats for three months significantly decreased blood pressure but did not completely normalize it. The increase in cardiac mass observed in spontaneously hypertensive rats was not reversed by this short treatment. Nevertheless, the percentage of the V1 form of myosin increased slightly after treatment, and the collagen content of the left ventricle was considerably decreased. Converting enzyme inhibition did not decrease blood pressure in DOCA-salt hypertension, and no changes were observed in cardiac hypertrophy, isomyosin profile, or the collagen network. The cardiac hypertrophy that occurs with aging in normotensive rats was associated with a significant shift in isomyosin profile and a large accumulation of collagen. Thus, aging mimics several of the quantitative and qualitative changes in the left ventricular protein profile observed in hypertension. In young normotensive rats, converting enzyme inhibition significantly decreased blood pressure and left ventricular mass, increased the percentage of V1 isomyosin, and prevented the accumulation of collagen. In one-year-old normotensive rats, treatment for six months with converting enzyme inhibitor decreased blood pressure, decreased cardiac mass, and prevented the accumulation of collagen; the isomyosin profile was not modified. Converting enzyme inhibition, by acting on cardiac afterload, can bring about quantitative and qualitative changes in the cardiac proteins of both hypertensive and normotensive rats.
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PMID:Myocardial effect of converting enzyme inhibition in hypertensive and normotensive rats. 297 59

Cardiac function in rat renal hypertension has been shown repeatedly to be depressed. The reason for this impairment has not been fully understood, although cardiac hypertrophy and increased collagen content have been claimed as possible causes. To further unravel the mechanisms underlying the deterioration of left ventricular function in rat renal hypertension, we investigated cardiac function, myocardial morphology, myosin iso-enzymes, plasma renin activity and levels of myocardial high-energy compounds in hearts from rats exposed to renal and reversed renal hypertension. Maximal cardiac function was unaltered in hearts exposed to antihypertensive therapy from the time of renal artery clipping compared with untreated hypertensive rats. The observed alterations of iso-enzyme pattern, plasma renin activity levels and myocardial morphology among the groups showed to be of less importance with respect to cardiac performance. Together with previous results from our laboratory, the present findings suggest that some negative inotropic agent of renal or non-renal origin is released during two-kidney, one clip renal hypertension, which counteracts the enhanced left ventricular performance induced by cardiac hypertrophy.
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PMID:Mechanisms behind myocardial depression in rat renal hypertension. 297 51


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