Atrial Natriuretic Peptide in Heart Failure

Summary

The secretion of atrial natriuretic peptide (ANP) in heart failure is increased. Its potential beneficial effects in heart failure are due to a reduction of volume and load of the heart through its vasodilatory, diuretic and natriuretic properties. In patients with severe congestive heart failure pharmacologic doses of intravenous infusions of ANP improve ventricular function by reducing pre- and afterload. In patients with heart failure ANP suppresses the secretion of aldosterone and to a small extend of cortisol leaving plasma levels of renin, norepinephrine, prostacyclin and prostaglandin E₂ unchanged. The diuretic and natriuretic effects of ANP in heart failure are however considerably attenuated. Similar results have been obtained in animal models of heart failure studying hemodynamic, neurohumoral and renal changes over a whole dose response curve using unfusion rates which increase plasma levels of ANP within the pathophysiologic and pharmacologic range.

There is evidence from animal studies in experimental models of heart failure, that ANP may be important in the pathogenesis of cardiac failure in the early phase of the disease where ANP may suppress the activity of the renin-angiotensin-aldosterone system. In later phases of heart failure these effects of ANP are overridden most likely by more severe circulatory impairment which causes an increase of vasoconstrictory mechanisms like the renin-angiotensin-aldosterone system and vasopressin. In con trast to the early phase of heart failure where peripheral vascular resistance, renal blood flow and renal vascular resistance are not increased, the activation of vasoconstrictor mechanisms increase peripheral vascular resistance and renal vascular resistance and decreases renal blood flow. The attenuation of the renal effects of ANP in heart failure are possibly due to the different hemodynamic conditions especially within the kidneys, to a reduction of specific binding sites for ANP or possibly due to a rapid degradation of ANP within the kidneys. Counter-regulating neurohumoral systems may also be important like the renin-angiotensin-system, sympathetic nerve activity and vasopressin.