title: Neurohumoral blockade in CHF management.
abstract: Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of natriuretic peptides, endothelin and vasopressin, play key roles in the progression of CHF. In this context, agents targeting neurohormones offer a highly rational approach to CHF management, with ACE inhibitors, aldosterone antagonists and beta-adrenergic blockade improving the prognosis for many patients. Although relevant improvements in clinical status and survival can be achieved with these drug classes, mortality rates for patients with CHF are still very high. Moreover, most patients do not receive these proven life-prolonging drugs, partially due to fear of adverse events, such as hypotension (with ACE inhibitors), gynaecomastia (with spironolactone) and fatigue (with beta-blockers). New agents that combine efficacy with better tolerability are therefore needed. The angiotensin II type 1 (AT(1))-receptor blockers have the potential to fulfil both these requirements, by blocking the deleterious cardiovascular and haemodynamic effects of angiotensin II while offering placebo-like tolerability. As shown with candesartan, AT(1)-receptor blockers also modulate the levels of other neurohormones, including aldosterone and atrial natriuretic peptide (ANP). Combined with its tight, long-lasting binding to AT(1)-receptors, this characteristic gives candesartan the potential for complete blockade of the RAAS-neurohormonal axis, along with the great potential to improve clinical outcomes.
authors.affiliation: Franz-Volhard-Klinik, Humboldt-University, Berlin, 13125, Germany. willenbrock@fvk-berlin.de
authors.forename: R
authors.initials: R
authors.lastname: Willenbrock
authors.forename: S
authors.initials: S
authors.lastname: Philipp
authors.forename: V
authors.initials: V
authors.lastname: Mitrovic
authors.forename: R
authors.initials: R
authors.lastname: Dietz
mesh_terms: D000450:Aldosterone / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006727:Hormone Antagonists / Q000627:therapeutic use*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D012084:Renin-Angiotensin System / Q000502:physiology; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D006727:Hormone Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D018377:Neurotransmitter Agents; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D000450:Aldosterone; C081643:candesartan