Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure.
ABSTRACT The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of cardiovascular homeostasis. It has recently been demonstrated that endogenous RAS exist in target tissues that are important in cardiovascular regulation. This article reviews the multiple effects of angiotensin II in target tissues, the evidence for the presence of functional tissue RAS and the data that suggest a role for these tissue RAS in the pathophysiology of heart failure. Activation of circulating neurohormones is predictive of worsened survival in heart failure; however, cardiac and renal tissue RAS activities are also increased in the compensated stage of heart failure, when plasma renin-angiotensin activity is normal. It is hypothesized that the plasma RAS maintains circulatory homeostasis during acute cardiac decompensation, while changes in tissue RAS contribute to homeostatic responses during chronic sustained cardiac impairment. This concept of different functions of circulating and tissue RAS in the pathophysiology of heart failure may have important pharmacologic implications.
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ABSTRACT: Most patients hospitalized for acutely decompensated heart failure (ADHF) present with symptoms and signs of volume overload, which is also associated with substantially high rates of death and rehospitalization in ADHF. To review the recent experimental and clinical evidence on existing therapeutic algorithms and investigational drugs used for the treatment of volume overload in ADHF patients. A systematic search of peer-reviewed publications was performed on Medline and EMBASE from January 1990 to March 2012. The results of unpublished trials were obtained from presentations at national and international meetings. Apart from intrinsic renal insufficiency and neurohormonal activation, volume overload through venous congestion may be the primary haemodynamic factor triggering the worsening of renal function in ADHF patients. It is well known that heart and kidneys are closely interrelated and an acute or chronic disorder in one organ may induce acute or chronic dysfunction in the other organ. Established therapeutic strategies, (e.g. loop diuretics, vasodilators, and inotropes), are sometimes associated with limited clinical success due to tolerance and the need for frequent up titration of the doses in order to achieve the desired effect. That leads to an increasing interest in novel options, such as the use of adenosine A1 receptor antagonists, vasopressin antagonists, and renal-protective dopamine. Initial clinical trials have shown quite encouraging results in some heart failure subpopulations but have failed to demonstrate a clear beneficial role of these agents. On the other hand, ultrafiltration appears to be a more promising therapeutic procedure that will improve volume regulation, while preserving renal and cardiac function. Further clinical studies are required in order to determine their net effect on renal function and potential cardiovascular outcomes. Until then, management of volume overload in ADHF patients remains a challenge for the clinicians.European heart journal. Acute cardiovascular care. 09/2012; 1(3):256-68.
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ABSTRACT: The incidence of heart failure and renal failure is increasing and is associated with poor prognosis. Moreover, these conditions do often coexist and this coexistence results in worsened outcome. Various mechanisms have been proposed as an explanation of this interrelation, including changes in hemodynamics, endothelial dysfunction, inflammation, activation of renin-angiotensin-aldosterone system, and/or sympathetic nervous system. However, the exact mechanisms initializing and maintaining this interaction are still unknown. In many experimental studies on cardiac or renal dysfunction, the function of the other organ was either not addressed or the authors failed to show any decline in its function despite histological changes. There are few studies in which the dysfunction of both heart and kidney function has been described. In this review, we discuss animal models of combined cardiorenal dysfunction. We show that translation of the results from animal studies is limited, and there is a need for new and better models of the cardiorenal interaction to improve our understanding of this syndrome. Finally, we propose several requirements that a new animal model should meet to serve as a tool for studies on the cardiorenal syndrome.Heart Failure Reviews 09/2011; 17(3):411-20. · 4.45 Impact Factor
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ABSTRACT: Acute decompensated heart failure (ADHF) with associated volume overload is the most common cause of hospitalization in heart failure patients. When accompanied by worsening renal function, it is described as a cardiorenal syndrome and is a therapeutic challenge. Initial treatment commonly encompasses intravenous diuretics however, suboptimal results and high rehospitalization rates have led experts to search for alternative therapeutic strategies. Recent technological advances in extracorporeal therapies have made ultrafiltration a feasible option for treatment of hypervolemia in ADHF. Recent large randomized trials have compared the efficacy and safety of ultrafiltration with diuretics. Additionally, the benefits of novel pharmacologic approaches, including combining hypertonic saline with diuretics, have recently been studied. The aim of this review is to discuss the developments in both pharmacologic and extracorporeal methods for treating hypervolemia in ADHF and acute cardiorenal syndrome.Current Heart Failure Reports 01/2013;