Vasoconstrictor Mechanisms and the Effects of Nitrates

Abstract

Studies on the peripheral circulations in congestive heart failure have indicated that vasomotor tone is increased (1–3). Certainly, vasoconstriction is the hallmark of advanced biventricular failure; however, vasoconstriction is not always present, all the time, in all patients, and in all regional vascular beds. The state of the circulation in heart failure will depend on the stimulus for heart failure and its severity, and where in the time course of congestive failure the patient or animal model is studied. In addition, the state of the circulation is also dependent upon endogenous (exercise) or exogenous stress (environmental temperature). These factors work to alter the state of the circulation via normal physiological mechanisms (reflexes, hormones) operating normally or in excess, or by nonphysiologial mechanisms peculiar to heart failure. In general, the vasoconstriction of far-advanced congestive heart failure can be related to four primary factors: (a) increased neurogenic sympathetic vasoconstrictor tone; (b) increased circulating levels of norepinephrine; (c) increased circulating levels of angiotensin II; and (d) mechanical factors impeding vascular relaxation (increased vascular sodium content, increased interstitial pressure). This brief review will consider how these factors mediate the development of vasoconstriction in heart failure, how they affect the distribution of blood flow to the arterial beds at rest and during exercise, the consequences of this blood flow redistribution, and the role these factors play in determining venous capacitance. Lastly, the effects of nitrate administration on this complex system will be considered. More thorough reviews of cardiac and circulatory compensatory mechanisms in heart failure are published elsewhere (1–4).

This work was supported in part by grants from the National Heart, Lung, and Blood Institute, HL 23836 and HL 25186