Benefits of prolonged angiotensin-converting enzyme inhibition in congestive heart failure.
Normal individuals have time-dependent variations in cardiovascular function, most of which are circadian (once daily). They include changes in heart rate, systemic arterial blood pressure, cardiac output, blood volume, and viscosity. There are also changes in neuroendocrine function, including the sympathetic and parasympathetic nervous systems and the renin-angiotensin system. These variations have important consequences for the heart, since haemodynamic and neuroendocrine alterations determine cardiac work load; heart rate, blood pressure, and sympathetic nervous system activity are highest during the waking hours and lowest during sleep. Cardiovascular mortality and morbidity are associated with these changes. Patients with congestive heart failure undergo changes in neurohumoral cardiovascular regulation that increase the work load of the heart as a result of increases in heart rate and peripheral vascular resistance. Moreover, a normal circadian variation is lost, causing blood pressure and heart rate to remain increased at night, depriving the heart of a period of rest. In addition, these patients have an ability to increase blood flow to exercising skeletal muscle, limiting exercise tolerance, as well as the consequences of elevated ventricular filling pressures. These time-dependent variations in the pathophysiological processes of congestive heart failure have implications for pharmacological therapy. In particular, vasodilator therapy should be administered to provide optimal unloading of the heart throughout the day. Vasodilator therapy should also provide antagonism to those factors that limit blood flow to working skeletal muscle, so that the physical ability is not intermittently compromised during the trough effect of the drug. Criteria for establishing the efficacy of drugs for the treatment of congestive heart failure should include an analysis of peak and trough effects.
Department of Medicine, Tulane University School of Medicine, New Orleans, La.
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Giles
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000145:classification / Q000627:therapeutic use*; D002940:Circadian Rhythm; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D018377:Neurotransmitter Agents / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents