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)

Throughout the course of chronic congestive heart failure cardiac and peripheral compensatory mechanisms are at play, most of them under the influence of the neuroendocrine system. The reserves of heart rate and contractility are regulated essentially by the noradrenergic system (NAS), but this mechanism is partial and transient owing to the gradual decrease in the density and sensitivity of myocardial beta-adrenergic receptors induced by overstimulation. Adaptation of the heart to exercise may be reduced. This escape phenomenon is also observed with almost all cardiotonic drugs which interfere with cyclic adenosine monophosphate (cAMP), in contrast with the paradoxically favourable effects of beta-blockers in small doses or of drugs that are both agonists and antagonists of beta-adrenergic receptors. The mechanisms which contribute to the induction of left ventricular hypertrophy are imperfectly known. The noradrenergic system and the renin-angiotensin-aldosterone system (RAAS) are probably not the only ones involved. The setting in action of Frank-Sterling heterometric regulation, at first during exercise then permanently, requires an increase in filling pressure obtained by venous constriction (predominantly controlled by the NAS) and, mostly, by an increase in circulating blood volume. NAS and RAAS intervene in the kidneys to produce water-and-salt retention.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Neuroendocrine changes in chronic cardiac insufficiency]. 296 69

With physiologic stress to the cardiovascular system, some circulatory compensatory mechanisms are designed to restore homeostasis quickly (e.g., sympathetic nervous system activation and the Frank-Starling mechanism). These compensatory mechanisms are not nearly as effective when there is a chronic pathologic stress such as congestive heart failure (CHF). In this circumstance, other mechanisms that operate with longer time constants come into play (e.g., activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and deconditioning). The most successful chronic drug therapies of CHF are those that are designed to reverse the latter group of compensatory mechanisms, a process that is slow. It takes especially long to reverse those CHF-induced changes in blood vessels and skeletal muscle metabolism that are activated to cope with inadequate delivery of oxygenated blood to working muscles. The concept that compensatory mechanisms have either short or long time constants for activation, effectiveness and reversal may help explain why the improvement in exercise tolerance with effective heart failure therapy lags behind hemodynamic improvement.
 ...
PMID:Regional blood flow in congestive heart failure: concept of compensatory mechanisms with short and long time constants. 297 Jul 84

Cardiac (or myocardial) failure, a major health problem, can be defined using physiologic criteria that consider the adequacy of O2 delivery relative to the body's O2 requirements. In clinical terms, cardiac failure may be described in terms of its chronicity or the extent to which signs and symptoms of right- versus left-sided heart failure are dominant. Congestive heart failure is a clinical syndrome that consists of a constellation of signs and symptoms that arise from congested organs and hypoperfused tissues. Acute cardiac failure occurs because of a decrease in myocardial contractility that can be offset by the Frank-Starling mechanism. In chronic cardiac failure dilatation and myocardial hypertrophy serve to restore ventricular function. Other compensatory responses that are invoked include a salt avid kidney, which mediates an expansion of the intravascular space, and the activation of the adrenergic nervous and renin-angiotensin-aldosterone systems and an increase in circulating arginine vasopressin. The management of acute and chronic cardiac failure can be derived from an understanding of the pathophysiologic mechanisms responsible for their appearance and include improving cardiac performance, as well as the distribution of systemic blood flow to tissues based on physiologic priorities and moment to moment variations in O2 requirements.
 ...
PMID:Pathophysiology of acute and chronic cardiac failure. 361 18

The Framingham heart study has shown that arterial hypertension is the major aetiological factor for the development of heart failure. In the presence of heart failure, various regulatory systems may be operative. These include the Frank-Starling mechanism, the neurohormonal system, regulation of cardiac growth and peripheral oxygen delivery. Recently, the interrelationship of the neuroendocrine system and cardiac growth has been examined. In the pressure or volume overloaded heart, growth of the myocardium involves the enlargement of cardiac myocytes, an adaptation governed by ventricular loading. Non-myocyte cell growth, including cardiac fibroblasts, may also occur. However, the haemodynamic load does not appear to be its major physiological stimulus. Cardiac fibroblast activation is responsible for the accumulation of type I and III collagens, the major fibrillar proteins of the myocardial collagen matrix, while vascular smooth muscle cell growth accounts for medial thickening of coronary resistance vessels. This structural remodelling of the cardiac interstitium represents a major determinant of pathological hypertrophy: it accounts for abnormal myocardial stiffness and impaired coronary reserve, thereby leading to ventricular diastolic and systolic dysfunction and ultimately the appearance of symptomatic heart failure. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems are involved in the structural remodelling of the non-myocyte compartment, including the 'cardioprotective' effects of angiotensin converting enzyme (ACE) inhibition or the beneficial effects of anti-aldosterone treatment that were found to prevent myocardial fibrosis in renovascular hypertension due to unilateral renal ischaemia under experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of the structural remodelling of the myocardium: from hypertrophy to heart failure. 771 13

According to the Framingham Study, arterial hypertension and coronary artery disease are the major etiologic factors in the development of heart failure. Regulatory systems that may affect heart failure include the Frank-Starling mechanism, neurohormonal responses, cardiac growth and peripheral oxygen delivery. Recently, the interrelationship between the neuroendocrine system and cardiac growth has aroused much interest. In the pressure- or volume-overloaded heart, hypertrophic growth of the myocardium includes the enlargement of cardiac myocytes, an adaptation governed by ventricular loading. Nonmyocyte cell growth involving cardiac fibroblasts may also occur but is not primarily regulated by the hemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intramyocardial coronary arteries, while vascular smooth muscle cell growth accounts for the medial thickening of these vessels. This remodeling of the cardiac interstitium is a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness and impaired coronary vasodilator reserve, leading to ventricular diastolic and systolic dysfunction and, ultimately, symptomatic heart failure. Several lines of evidence suggest that the renin-angiotensin-aldosterone system is involved in regulating the structural remodeling of the nonmyocyte compartment; this accounts for the cardioprotective effects of angiotensin converting enzyme (ACE) inhibition, which prevents myocardial fibrosis in rats with renovascular hypertension. In rats with genetic hypertension, established left ventricular hypertrophy, abnormal diastolic stiffness due to interstitial fibrosis and reduced coronary vasodilator reserve associated with medial wall thickening of intramyocardial resistance vessels, the ACE inhibitor lisinopril restored myocardial structure and function towards normal.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The cardiac structure-function relationship and the renin-angiotensin-aldosterone system in hypertension and heart failure. 782 69

In the presence of a primary disorder in myocardial contractility and/or extraordinary hemodynamic pressure on the heart, ventricular performance depends on several compensating mechanisms. In the past, studies were mostly focused on the importance of the Frank-Starling mechanism and the hypertrophy and dilation of the heart in maintaining a circulation sufficient for metabolic intake during heart failure. Recently, however, the existence of neurohormonal systems has been demonstrated (the sympathetic nervous system, the renin-angiotensin system, atrial natriuretic peptide and several locally produced vasoactive substances), which change considerably according to the severity of the heart failure. While these compensatory mechanisms support the circulation in patients with acute heart failure, in whole or in part, neurohormonal activation over an extended period of time might be harmful to patients with chronic congestive heart failure since several neurohormonal factors might be inappropriately activated. This article will review the key neurohormonal systems and their importance in heart failure on the basis of the current literature.
 ...
PMID:Neurohormonal systems during progression of heart failure: a review. 790 8

The maintenance of cardiac pumping ability in the presence of a primary disturbance of myocardial contractility and/or an excessive haemodynamic strain on the heart is dependent on several compensatory mechanisms. Particular attention has formerly been paid to the importance of the Frank-Starling mechanism and cardiac hypertrophy and dilatation in maintaining a blood supply sufficient to cover the metabolic needs of various tissues in heart failure. In recent years, however, it has been found that certain neurohormonal systems (the sympathetic nervous system, the renin-angiotensin-aldosterone system, atrial natriuretic peptide and several locally acting vaso-active substances) undergo considerable changes according to the degree of heart failure. These compensatory mechanisms support the circulation wholly or partially in acute heart failure, however sustained neurohormonal activation may be harmful in chronic heart failure, where several neurohormonal factors may be activated to ill-effect. The most significant neurohormonal systems and their importance in heart failure are reviewed on the basis of the available literature.
 ...
PMID:[Neurohormonal activity in heart insufficiency]. 831 27

In chronic heart failure, various regulatory systems including the Frank-Starling mechanism, the neuro-hormonal response, cardiac growth and peripheral oxygen delivery may be operative. Recently, the inter-relationship of the renin-angiotensin-aldosterone system (RAAS) and cardiac growth has drawn clinical interest. In the pressure-or volume-overloaded heart, the development of myocyte growth is primarily dependent on ventricular loading. Non-myocyte cell growth involving cardiac fibroblasts may also occur but this is not primarily regulated by the haemodynamic load. Cardiac fibroblast activation is responsible for the accumulation of fibrillar type I and type III collagens within the interstitium and adventitia of intramyocardial coronary arteries. In addition to relaxation abnormalities due to impairment of sarcoplasmic Ca(2+)-ATPase activity, this remodelling of the cardiac interstitium represents a major determinant of pathological hypertrophy in that it accounts for abnormal myocardial stiffness, leading to ventricular diastolic and systolic dysfunction and ultimately the progression of symptomatic heart failure. The effector hormones of the RAAS, angiotensin II (AngII) and aldosterone (Aldo), appear to be primarily involved in promoting the adverse structural remodelling of the myocardial collagen matrix. In cultured adult cardiac fibroblasts, AngII and Aldo have been shown to stimulate collagen synthesis while AngII additionally inhibits matrix metalloproteinase I activity, which is the key enzyme for degradation of fibrillar collagen in the cardiac interstitium, leading to excessive collagen accumulation. These findings may serve as rationale as to why angiotensin converting enzyme inhibition or blockade of the RAAS represents such remedial therapy beyond the effect of simply unloading the heart in patients with congestive heart failure.
 ...
PMID:The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure. 868 74

Chronic myocardial ischemia is the leading cause of disturbances in myocardial contractility (myocardial infarction) or hemodynamic overload upon the left ventricle. The heart reactions consist in a series of adaptative mechanisms in order to maintain its pump function: Frank-Starling mechanism, myocardial hypertrophy and neurohumoral activation. In heart failure, the cardiac output is maintained by an increase of the preload which enhances the contractility (Frank-Starling law). Myocardial ischemia influences the systolic and diastolic function. The decrease of cardiac output leads to neurohumoral responses which, in the initial stages of cardiac failure are compensatory; along with the progression of the disease, they exert adverse effects. Increased activity of the sympathetic nervous system induces high cardiac rates, chronotropic incompetence. Activation of the renin-angiotensin system held to myocardial and vascular hypertrophy, vasoconstriction, fluid retention. Endothelin is the most powerful vasoconstrictor; its plasmatic concentrations correlate with the severity of the disease. Vasodilator mediators released in cardiac failure are the natriuretic peptide, nitric oxide, dopamine, prostacicline, bradikinin.
 ...
PMID:[Heart failure due to ischemia--the adaptive mechanisms]. 1075 79

Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it also has effects on contractility. The interaction of endothelin-1 and the Frank-Starling response is unknown. The present study aimed to characterize the role of endothelin-1 in the regulation of the Frank-Starling response, one of the major mechanisms regulating cardiac contractile force, in both normal and hypertrophied hearts. Nontransgenic rat hearts and hypertrophic hearts of hypertensive double transgenic rats harboring human angiotensinogen and renin genes were studied in a Langendorff isolated heart setup with a liquid-filled balloon inside the left ventricle used to measure contractile parameters. The rats were studied at compensated phase, before showing any signs of heart failure. Compensated hypertrophy in double transgenic rat hearts resulted in improved contractility at a given level of preload when compared with nontransgenic rat hearts. Hearts of both rat lines showed preserved Frank-Starling responses, that is, increased contractile function in response to increased end-diastolic pressure. The mixed endothelin A/B receptor antagonist bosentan attenuated the Frank-Starling response by 53% (P<0.01) in the double transgenic hearts but not in nontransgenic hearts. The diastolic parameters remained unaffected. The left ventricles of the double transgenic rat hearts showed an 82% higher level of endothelin type A receptor mRNA and a 25% higher level of immunoreactive endothelin-1 compared with nontransgenic rat hearts. The type 1 angiotensin II receptor antagonist CV-11974 had no significant effect on contractile function in response to load in either strain. These results show that endogenous endothelin-1 contributes to the Frank-Starling response in hypertrophied rat hearts by affecting systolic performance.
 ...
PMID:Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts. 1251 36


<< Previous 1 2