Regulation of cardiac preload by atrial natriuretic peptide in congestive cardiac failure.
Plasma atrial natriuretic peptide levels are increased in heart failure. In rats with experimental heart failure, the elevation in plasma atrial natriuretic peptide bore a close relationship to the size of the myocardial infarct and the degree of ventricular dysfunction. Sodium retention, assessed by changes in exchangeable body sodium, could not be demonstrated in this model of cardiac dysfunction. Even rats receiving a low-sodium diet had increased plasma atrial natriuretic peptide levels following coronary artery ligation despite a significant decrease in exchangeable body sodium. This establishes that the elevated plasma atrial natriuretic peptide levels found in heart failure are a consequence of ventricular dysfunction and increased intracardiac pressures rather than a reflection of the salt and water status. Alternatively, the elevated plasma atrial natriuretic peptide may limit salt and water retention in this model. In these animals with high circulating atrial natriuretic peptide levels, "down-regulation" of renal atrial natriuretic peptide receptors could be demonstrated. This decrease in renal atrial natriuretic peptide receptor numbers may, in part, explain the blunted response to infused atrial natriuretic peptide in heart failure. However, changes in renal atrial natriuretic peptide receptors alone would appear to be insufficient to lead to salt and water retention without the activation of other sodium-retaining mechanisms that occur with the progression of cardiac failure. Nevertheless, this down-regulation of renal atrial natriuretic peptide may then contribute to the salt and water retention that occurs in congestive biventricular heart failure. The close relationship between increases in atrial natriuretic peptide and ventricular dysfunction rather than sodium balance suggests that atrial natriuretic peptide's primary role in the circulation may be to produce venodilation and increase capillary permeability. This may act rapidly to reduce cardiac preload and prevent pulmonary congestion. Vasodilation and natriuresis may then become supplementary actions to maintain cardiac output and remove the excess fluid.
Johnston
C I
CI
University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Hodsman
G P
GP
Harrison
R W
RW
Mendelsohn
F A
FA
Tsunoda
K
K
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000378:metabolism; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D012964:Sodium; D012083:Renin; D017461:Receptors, Atrial Natriuretic Factor