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Regulation of cardiac preload by atrial natriuretic peptide in congestive cardiac failure
C I Johnston1, G P Hodsman, R W Harrison
1University of Melbourne Department of Medicine, Austin Hospital, Heidelberg, Victoria, Australia.
Insights
Elevated plasma atrial natriuretic peptide in heart failure is linked to ventricular dysfunction, not sodium levels. This peptide may initially reduce fluid retention, but receptor changes can contribute to salt retention in advanced heart failure.
Area of Science:
- Cardiology
- Endocrinology
- Physiology
Background:
- Plasma atrial natriuretic peptide (ANP) levels increase in heart failure.
- The relationship between ANP, ventricular dysfunction, and sodium balance in heart failure requires clarification.
Purpose of the Study:
- To investigate the relationship between plasma ANP levels, myocardial infarct size, and ventricular dysfunction in a rat model of heart failure.
- To determine if elevated ANP in heart failure is a consequence of sodium/water status or ventricular dysfunction.
- To explore the role of renal ANP receptors in the context of heart failure and ANP levels.
Main Methods:
- Induction of experimental heart failure in rats via coronary artery ligation.
- Measurement of plasma atrial natriuretic peptide levels.
- Assessment of sodium retention using exchangeable body sodium.
- Evaluation of renal atrial natriuretic peptide receptor expression.
Main Results:
- Elevated plasma ANP levels correlated closely with myocardial infarct size and ventricular dysfunction.
- Sodium retention was not demonstrated in this model, even with a low-sodium diet.
- Down-regulation of renal ANP receptors was observed in animals with high circulating ANP levels.
- The blunted response to infused ANP in heart failure may be partly explained by decreased receptor numbers.
Conclusions:
- Elevated plasma ANP in heart failure is primarily driven by ventricular dysfunction and increased intracardiac pressures, rather than altered sodium balance.
- While ANP may initially limit salt/water retention, down-regulation of renal receptors could contribute to fluid retention in advanced congestive heart failure.
- The primary role of ANP in heart failure circulation might be venodilation and increased capillary permeability to reduce preload and prevent pulmonary congestion.
Abstract:
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.