7 Atrial natriuretic peptide: Water and electrolyte homeostasis

Summary In the few years since its identification, a clear role for ANP in the regulation of water and electrolyte balance has emerged (Figure 3). The peptide is released in response to blood volume expansion, both acutely and gradually during changes in dietary sodium intake. Similarly, plasma levels are elevated in pathophysiological conditions such as cardiac and renal failure. It has become apparent that ANP has natriuretic, diuretic and vasorelaxant properties. Many of the original studies employed what we now know to be pharmacological doses of the peptide. However, recent reports have confirmed that small, sustained elevations in plasma ANP within or marginally above the ‘normal' physiological range produce similar effects. A number of recent studies have tried to specifically address the physiological relevance of ANP. Although undoubtedly released by atrial distension and effective when infused to similar concentrations, atrial distension also has other effects via neural pathways. Thus, the demonstration that excretion of saline is impaired by atrial appendectomy (Benjamin et al, 1988) does not imply that this is only due to the absence of an atrial hormone. Goetz et al (1986) demonstrated that in the denervated heart, although ANP is still released, the excretion of a saline load is impaired. Similarly, in man, Richards et al (1988a) needed to infuse ANP to much higher plasma levels than those achieved by a saline load in order to reproduce the natriuresis. Although these experiments can be criticized, they confirm that ANP is not the sole mechanism for excreting a volume load, or for the natriuresis following atrial distension, but that these effects are likely to reflect the balance between ANP, AVP, the renin—angiotensin and autonomic nervous systems. In rats immunized against ANP (Greenwald et al, 1988), although the ability to excrete an acute saline load was impaired, long-term sodium balance was normal, suggesting that the rats were able to compensate for the absence of ANP. Many of the actions of ANP can be explained by antagonism of the renin—angiotensin—aldosterone system. Teleologically, it seems appropriate that a natriuretic hormone should counterbalance the major pressor and antinatriuretic hormones within the body. There is good evidence for cellular interactions between angiotensin, AVP, aldosterone and ANP at a number of discrete sites which are additional to the straightforward physiological antagonism of systems with opposing actions. ANP inhibits aldosterone secretion directly and may also reduce renal renin release. In the vascular tree there is evidence that ANP specifically blocks the vasoconstrictor actions of angiotensin II and possibly AVP. Vascular receptors for ANP and angiotensin II are similarly distributed, and angiotensin II can independently regulate the ANP receptor. In the kidney ANP antagonizes the action of angiotensin on glomerular permeability and vasa recta blood flow, and there is evidence of mutual antagonism with respect to regulation of sodium excretion. Finally in the central nervous system ANP opposes the dipsogenic effects of angiotensin and can inhibit AVP secretion. In the few years since its discovery, the physiological actions of ANP have been established and, although not as powerful as initial experiments suggested, they are ideally placed to oppose the major antidiuretic and antinatriuretic hormonal systems.