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

Vasovagal syncope is defined as a reflex loss of consciousness related to reaction to various stimuli as orthostatic stress, pain or emotions connected with loss of muscle postural tone. The aetiology of this disorder is still unknown. The imbalance between the parts of autonomic nervous system and other homeostasis-related systems as renin-angiotensin-aldosterone system, peptides as endothelin, neuropeptide Y, vasopressin, adrenomedullin and cAMP, adenosine and AMP can play an important role in the development of vasovagal syncope. In the first part of the paper the authors describe the mechanisms involved in the development of vasovagal reaction, pathophysiology of the head-up tilt test and the role of autonomic nervous system.
 ...
PMID:[Neurohumoral mechanisms for vasovagal syncopes. Part I]. 1286 5

Acute administration of adrenomedullin (AM) exerts beneficial hemodynamic, renal, and neurohormonal effects in heart failure (HF). However, chronic effects of AM administration on HF remain unknown. This study sought to examine the effect of chronic infusion of AM on progression of HF in rat. Human recombinant AM was administered by osmotic minipump for 7 weeks in the HF model of Dahl salt-sensitive rats. The effect was compared with vehicle and diuretic treatment group. Chronic AM infusion significantly decreased left ventricular end-diastolic pressure, right ventricular systolic pressure, right atrial pressure, and left ventricular weight/body weight (P<0.01 for all). AM significantly attenuated the increase in circulating renin-aldosterone, endogenous rat AM, and atrial natriuretic peptide levels (P<0.01 for all). AM also inhibited the myocardial tissue levels of angiotensin II and atrial and brain natriuretic peptide (P<0.01 for all). These changes were associated with the improvement of cardiac output and systemic vascular resistance (both P<0.05). Furthermore, AM improved left ventricular end-systolic elastance (P<0.01). These improvements were greater in the AM than in the diuretic group, although both drugs similarly decreased systolic blood pressure and increased urinary sodium excretion. Kaplan-Meier survival analysis showed that AM significantly prolonged survival time compared with diuretic (P<0.05) and vehicle (P<0.01) treatment groups. These results suggest that endogenous AM plays a compensatory role in HF and that chronic AM infusion attenuates progression of left ventricular dysfunction and improves survival, at least in part, through inhibition of circulating and myocardial neurohormonal activation.
 ...
PMID:Chronic administration of adrenomedullin attenuates transition from left ventricular hypertrophy to heart failure in rats. 1456 98

Several mouse models have already proved valuable for investigating hypertrophic responses to cardiac stress. Here, we characterize one caused by a well defined single copy transgene, RenTgMK, that genetically clamps plasma renin and thence angiotensin II at high levels. All of the transgenic males develop concentric cardiac hypertrophy with fibrosis but without dilatation. Over half die suddenly aged 6-8 months. Telemetry showed disturbances in diurnal rhythms a few days before death and, later, electrocardiographic disturbances comparable to those in humans with congestive heart failure. Expression of seven hypertrophy-related genes in this and two categorically different models (lack of atrial natriuretic peptide receptor A; overexpression of calsequestrin) were compared. Statistical analyses show that ventricular expressions of the genes coding for atrial natriuretic peptide, beta myosin heavy chain, medium chain acyl-CoA dehydrogenase, and adrenomedullin correlate equally well with the degree of hypertrophy, although their ranges of expression are, respectively, 50-, 30-, 10-, and 3-fold.
 ...
PMID:Cardiac hypertrophy and sudden death in mice with a genetically clamped renin transgene. 1497 80

In this paper we review pathophysiologic aspects of heart failure (HF). Mechanisms that normally act to prevent decrease in stroke volume and peripheral pressure are activated in HF and become maladaptive. These mechanisms lead to cardiac stimulation (inotropism, chronopism and lusotropism), peripheral vasoconstriction and sodium and water retention. HF progression is related to a) neurohumoral mechanisms, signaled by neurohumoral messengers; b) inflammatory activation; and c) ventricular remodeling that can be both cause and consequence of HF. We review the main neurohumoral mechanisms, some "regulators" (vasoconstrictors, antinatriuretics, inotropics and proliferatives) and some "counter-regulators" (vasodilators, natriuretics, negative inotropics and antiproliferatives). The first group includes the sympathetic nervous system, the renin angiotensin aldosterone system, arginine-vasopressive and endothelin, while in the second group natriuretic peptides, nitric oxide, bradykinin, vasodilator prostaglandins, the dopaminergic system, adrenomedullin and parasympathetic mechanisms are included. In inflammatory activation we review cytokines and oxidative stress. In ventricular remodeling we review modifications in myocyte function and morphology as well as modifications in the interstitium. Actions and interactions between these systems are the main factors leading to HF progression.
 ...
PMID:[Physiopathology of heart failure]. 1522 47

Adrenomedullin, a 52-amino acid residue peptide, has numerous biological actions which are of potential importance to cardiovascular homeostasis, growth and development of cardiovascular tissues and bone, prevention of infection, and regulation of body fluid and electrolyte balance. Studies in man using intravenous infusion of the peptide have demonstrated that, at plasma levels detected after myocardial infarction or in heart failure, adrenomedullin reduces arterial pressure, increases heart rate and cardiac output, and activates the sympathetic and renin-angiotensin systems but suppresses aldosterone. The thresholds for these responses differ, being lower under some experimental circumstances for arterial pressure than for the other biological effects. Adrenomedullin administration inhibits the pressor and aldosterone-stimulating action of angiotensin II in man. By contrast, the pressor effect of norepinephrine is little altered by concomitant adrenomedullin administration. Although in the absence of a safe, specific antagonist of the actions of endogenous adrenomedullin it is difficult to be certain about the physiological and pathophysiological importance of this peptide in man, current evidence suggests that it serves to protect against cardiovascular overload and injury. Hope has been expressed that adrenomedullin or an agonist specific for adrenomedullin receptors might find a place in the treatment of cardiovascular disorders.
 ...
PMID:Hemodynamic and hormonal actions of adrenomedullin. 1527 27

Arterial hypertension is a common disorder with a frequency of 10% to 15% in subjects in the 40- to 60-year age group. Yet most reports find the prevalence of arterial hypertension in patients with chronic liver disease (cirrhosis) much lower. In this review, we consider the alterations in systemic hemodynamics in cirrhosis. The most characteristic findings in cirrhotic patients are vasodilatation with low systemic vascular resistance, increased cardiac output, high arterial compliance, secondary activation of counterregulatory systems (sympathetic nervous system, renin-angiotensin-aldosterone system, neuropituitary release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through nitric oxide, calcitonin gene-related peptide, adrenomedullin, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance to increased arterial blood pressure. Subjects with established arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homeostatic regulation in cirrhotic patients with manifest arterial hypertension. This is a topic for future research.
 ...
PMID:Hypertension and liver disease. 1552 91

The so-called essential hypertension is not a single entity but a mixed bag with several polygenic quantitative traits acting in concert in different combinations in different individuals. This review collates all published information from different centres using different approaches to identify candidate genes in human hypertension. 1) gene targeting approach in animal models of HT (Smithies and Maeda, 1995); 2) identification of 874 candidate SNPs in 75 candidate genes for human HT (Halushka et al, 1999); 3) comparative genomic approach translating QTLs between rat and human HT, to identify 26 chromosome regions on 16 autosomes (Stoll M et al, 2000); 4) Ten centimorgan genome-wide scan done on 2010 affected sibling pairs drawn from 1599 severely hypertensive families (Caulfield et al, 2003). The molecular mechanisms of various molecules involved in the homeostasis of blood pressure are discussed. NO, O2, PG12, EDHF, endothelin, IL-6, selectin, phospholipase A2G1B, BH4, SOD, IRS-1, adrenomedullin, PAMP, CGRP, ANP, bradykinin and bombesin; adducin alpha, beta, gamma, SAH, renin, angiotensinogen. angiotensin II, aldosterone CYP11B1, mineralocorticoid receptors, 11betaHSD, DBH, PNMT, beta2adrenoreceptors, and genes related to ion transport-sodium-lithium cotransporters, ENaC, NaCl cotransporters NKCC2, KCNJ and NaKATPase. Altered gene expression in fetus due to maternal malnutrition also "programmes" for adult hypertension.
 ...
PMID:Hypertension: molecular approach. 1563 21

Exposure to LBNP results in body fluid shift to lower extremities similarly as under influence of orthostatic stress. In susceptible persons it leads to syncope. For better understanding why certain individuals are more susceptible to orthostatic challenges it seemed necessary to collect more data on hemodynamic and neuroendocrine adjustments occurring before onset of presyncopal symptoms Accordingly, in this study heart rate (HR), blood pressure (BP), stroke volume (SV), cardiac output (CO), hematocrit, plasma catecholamines, adrenomedullin, ACTH and plasma renin activity (PRA) were measured in 24 healthy men during graded LBNP (-15, -30 and -50 mmHg). Thirteen subjects completed the test (HT group) whereas 11 had presyncope signs or symptoms at -30 mmHg or at the beginning of -50 mmHg (LT group). Comparison of these groups showed that LT subjects had lower baseline total peripheral resistance and higher plasma adrenomedullin. During LBNP plasma catecholamine and PRA increases were even greater in LT than in HT group while plasma adrenomedullin elevations were similar in both groups. Plasma ACTH increased only in LT group following presyncope symptoms. Low tolerant group showed more rapid decline of SV and CO than HT subjects from the beginning of LBNP. It is suggested that measurements of SV at the level of LBNP which did not evoke any adverse symptoms may be of predictive value for lower orthostatic tolerance.
 ...
PMID:Hemodynamic and neuroendocrine predictors of lower body negative pressure (LBNP) intolerance in healthy young men. 1598 1

This review looks at the alterations in the systemic haemodynamics of patients with chronic liver disease (cirrhosis) in relation to essential hypertension and arterial hypertension of renal origin. Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counterregulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This provides an effective (although relative) counterbalance to raised arterial blood pressure. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development of chronic liver disease, and arterial hypertension is rarely manifested in patients with cirrhosis, even in those with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This probably includes the combination of vasodilatation and vasoconstriction in parallel.
 ...
PMID:Arterial hypertension and chronic liver disease. 1617 91

Four men established a new score (Guinness Book of Records) by staying submersed in thermoneutral water (average diving depth 2.5 m) for 41 h without sleeping. The aim of this study is to measure circulating hormones together with plasma mass density and total protein concentration as indices of plasma volume change to test the hypotheses that (1) blood volume and related hormones are influenced by prolonged water submersion the same way as observed after short-term water immersion, and (2) plasma adrenomedullin levels change in an opposite fashion as with orthostatic stimulation. We also studied effects on cortisol and testosterone levels. Water submersion led to a 19% increase in plasma protein concentration and a 2.5 g/l rise in plasma mass density, corresponding to a 15.6+/-1.1% plasma volume decrease (P=0.00). We therefore individually corrected (c) the observed post-submersion hormone values for plasma volume contraction. Based on this correction, we found a rise of plasma adrenomedullin from 7.9+/-0.9 to 12.5(c)+/-2.3 pg/ml. Aldosterone rose from 123+/-14 to 186(c)+/-24 ng/ml (P=0.029); plasma renin activity increased in all four persons but the type I error was >0.05. Plasma testosterone decreased from 3.5+/-0.4 to 2.2(c)+/-0.6 ng/ml (P=0.009) while plasma cortisol stayed unchanged. The daily salivary cortisol rhythm was preserved. We conclude that long-term water submersion has endocrine as well as plasma volume effects that are opposite to those seen after short-term immersion, and which increases plasma adrenomedullin. Circadian cortisol rhythm seems to be conserved even under extreme circumstances as those of this study.
 ...
PMID:Adrenomedullin and elements of orthostatic competence after 41 h of voluntary submersion in water as measured in four healthy males. 1641 51


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