title: Interrupting the adaptive changes in congestive heart failure.
abstract: Circulating plasma concentrations of norepinephrine, renin, angiotensin and vasopressin are increased in congestive heart failure. By increasing ventricular afterload, heart failure is further worsened, which in turn--in a vicious cycle--stimulates neurohumoral vasoconstrictor mechanisms. Furthermore, because of the compensatory but excessive stimulation of the sympathomimetic system, a down-regulation and desensitization particularly of the myocardial beta 1 receptors and depletion of myocardial catecholamine occurs in chronic heart failure. These defects may be restored toward normal by interventions that attenuate the activity of the sympathetic nervous system. A direct approach to modify the excessive vasoconstriction is to administer systemic vasodilator drugs, but despite favorable short-term effects, tolerance developed to most of these drugs during long-term treatment. One reason for the loss of effectiveness is the reflex activation of the sympathetic system, which increases vasoconstrictor hormone concentrations. Activation of the renin-angiotensin system can be modified effectively by angiotensin-converting enzyme inhibitors that have shown favorable responses in patients with chronic heart failure. Beta-blocking agents interfere with endogenous sympathetic activation and have produced beneficial effects in patients with congestive cardiomyopathy. Long-term treatment is associated with up-regulation of the number of beta receptors and an improved responsiveness to catecholamines. Owing to the negative inotropic effects of beta-blocking agents, some of the patients with severe heart failure deteriorated hemodynamically and clinically. Theoretically, it should be advantageous to have a substance that combines protection against excessive beta stimulation with a mild inotropic support to prevent cardiac decompensation. This may be achieved by a selective beta 1-partial agonist like xamoterol.
authors.affiliation: Department of Cardiology, Universitäts-Krankenhaus Eppendorf, Hamburg, Federal Republic of Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kupper
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D011311:Pressoreceptors / Q000502:physiology / Q000503:physiopathology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D017307:Xamoterol
chemical_list: D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D017307:Xamoterol