The relationship of the sympathetic nervous system and the renin-angiotensin system in congestive heart failure.
Congestive heart failure is a complex clinical syndrome characterized by circulatory and metabolic abnormalities. It has been apparent for more than 25 years that the sympathetic nervous system and the renin-angiotensin-aldosterone system are markedly activated in the late stages of heart failure. These two systems interact to facilitate sympathetic drive and promote salt and water retention. Circumstantial evidence is now accumulating to indicate that excessive sympathetic drive and angiotensin II activity may contribute to the pathophysiology of heart failure. These observations suggest that a dual strategy of modulating sympathetic nervous system activity to the heart while blocking angiotensin II activity may provide a rational therapeutic approach to the treatment of heart failure. Xamoterol, a beta 1 partial agonist, may enhance myocardial contractile force in the steady state, while acting to inhibit excessive sympathetic drive during exercise or severe heart failure. The concomitant use of a converting-enzyme inhibitor would be expected to blunt the detrimental effects of excessive angiotensin II activity. Modulation of adrenergic drive coupled with inhibition of marked angiotensin II activity may be potentially more effective in the treatment of congestive heart failure than either strategy used alone.
Francis
G S
GS
Department of Medicine, Veterans Administration Medical Center, Minneapolis, MN 55417.
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D011412:Propanolamines / Q000627:therapeutic use; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012084:Renin-Angiotensin System; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D017307:Xamoterol
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000804:Angiotensin II; D017307:Xamoterol