Congestive heart failure (CHF) promotes an array of biologic changes that are largely designed to compensate for reduced flow. These include activation of the sympathetic nervous system and the renin-angiotensin system, as well as the release of arginine vasopressin. The ultimate expression of these compensatory mechanisms is heightened vascular tone, increased sodium and water retention and antidiuresis. The peripheral circulation is normally under the fine control of circulating and neuronally released moieties, which can directly or indirectly alter vascular tone. Angiotensin II appears to be a key element in this regard because of its multiple biologic activities. Direct arteriolar vasoconstriction, facilitation of norepinephrine release and stimulation of aldosterone are some of the activities that are likely to be of major importance in the syndrome of CHF. Therefore, it is not surprising that converting enzyme inhibitors have a growing role as treatment. Other pharmacologic agents that can reduce sympathetic tone by acting on presynaptic receptors are being developed. Selective dilation of certain vascular beds may be possible with agents designed to interact with vascular dopaminergic receptors. The mechanisms whereby circulating epinephrine and norepinephrine modulate norepinephrine release and vascular tone are beginning to be understood and likely involve presynaptic, postsynaptic and nonsynaptic vascular receptors. A better appreciation of the mechanisms involved in the fine control of the peripheral circulation should allow for more selective and more imaginative pharmacologic therapy for CHF.
Bibliographical noteFunding Information:
From the Departments of Medicine, University of Minnesota Medical School and the Veterans Administration Medical Center, Minneapolis, Minnesota. This study was supported by Grants HL22977-03 and HL07184, from the National Heart, Lung, and Blood Institute, National lnstftutes of Health, Bethesda, Maryland, and a grant from the Veterans Administration Research Service, Washington, D.C.