Neuro-endocrine changes as new targets in the drug treatment of congestive heart failure.
The classical therapy of congestive heart failure (CHF) with inotropic agents (digitalis and newer inotropics) and diuretic agents remains unsatisfactory in many cases. More recently it is recognized, that some of the neuro-endocrine compensatory processes associated with CHF are detrimental in the long run, and therefore potentially targets for drug treatment. This holds for the following neuro-endocrine mechanisms: 1) increased activity of the sympathetic nervous system and high plasma catecholamines, accompanied by down-regulation of beta 1- but not beta 2-receptors in the heart; 2) stimulation of the renin-angiotensin-aldosterone system (RAAS), causing higher levels of renin, A II and aldosterone. The detrimental sequelae of both processes are even enhanced by their complex mutual interactions. Drug treatment aiming to reduce or suppress these processes and their negative results is potentially offered by: vasodilators, counteracting vasoconstriction, low dose selective beta 1-adrenoceptor blockers, which will not only impair tachycardia but also up-regulate cardiac beta 1-receptors and hence improve the inotropic response to catecholamines; aldosterone antagonists and ACE-inhibitors counteracting the activated RAAS. The beneficial effect of the ACE-inhibitors in CHF is well established and superior to that of classical vasodilators, since it additionally counteracts the enhanced RAAS activity.
van Zwieten
P A
PA
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects; D013565:Sympatholytics / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D013565:Sympatholytics; D014665:Vasodilator Agents; D009320:Atrial Natriuretic Factor