Atrial natriuretic peptide in congestive heart failure in the dog: plasma levels, cyclic guanosine monophosphate, ultrastructure of atrial myoendocrine cells, and hemodynamic, hormonal, and renal effects.

Abstract

In an animal preparation of congestive heart failure in the dog, during the development of cardiac failure due to rapid right ventricular pacing we observed significant decreases in cardiac output and arterial pressure and increases in pulmonary arterial and right atrial pressure. We also observed a related increase in right atrial pressure and increases in plasma levels of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (c-GMP). Ultrastructure changes in the atrial myoendocrine cells indicated extreme stimulation of the secretory apparatus of ANP. The response of hemodynamic, renal, and hormonal variables was investigated after incremental infusions (0.01, 0.03, 0.1, 0.3, and 0.6 ,ug/kg/min) of exogenous ANP. In healthy animals ANP significantly decreased mean arterial pressure, cardiac output, stroke volume, and right atrial pressure without changing heart rate or peripheral vascular resistance. As expected, we found a striking increase in urine flow and urinary excretion of sodium, chloride, magnesium and calcium and a smaller increase in potassium excretion. ANP suppressed renin secretion, and increased renal plasma flow, glomerular filtration rate, and filtration fraction. In dogs with heart failure ANP caused a small reduction in mean arterial pressure. No effect was seen on other hemodynamic variables or plasma renin concentration. The excretory effects on the kidneys were completely absent, and smaller increases in glomerular filtration rate and filtration fraction were observed. We found no difference between healthy dogs and animals with heart failure with respect to the secretion of c-GMP during ANP infusions in relation to the plasma levels of ANP. This suggests an intracellular defect that prevents the mediation of the hormonal signal into biological action in the presence of heart failure.Circulation 77, No. 2, 398-406, 1988 It has been shown3 that ANP is elevated in the presence of heart failure in proportion to the severity of the disease, suggesting that ANP may be important in the pathophysiology of cardiac failure. It has been reported that in patients with severe chronic congestive heart

Effects of Exogenous and Endogenous Natriuretic Peptides on Forearm Vascular Function in Chronic Heart Failure

“…Many studies have detailed the central hemodynamic, arterial, renal, and adrenal effects of exogenous [1][2][3][4][5][6][7][8] and endogenous 9 NPs in animal models of HF 1 and in human HF, 2-9 but little is known about the effects of NPs on the capacitance vasculature in this condition. In the present study, we assessed the effects of all 4 currently known human NPs on the forearm vasculature in matched groups of optimally treated cHF patients.…”

“…[1][2][3][4][5][6][7] Despite minimal effects on plasma volume and resistance vessel tone, infusion of NPs in patients with HF has consistently been shown to reduce central venous pressure (CVP). 8,9 This raises the possibility that the venodilator effects of NPs may be preserved in HF.…”

Sympathoadrenal inhibition by atrial natriuretic peptide is not attenuated during development of congestive heart failure in dogs.

“…A short duration of the pacing-induced ANP elevation, too short for down-regulating the ANP responses of the sympathoadrenal system, should not play a role; the pacing period lasted long enough to abolish the systemic-hemodynamic ANP effect (Figures 3 and 5) and to depress renal vascular responsiveness to ANP. 15 Furthermore, it appears unlikely that the large baseline changes of neuroendocrine parameters during chronic pacing (Table 2) would explain the increased ability of ANP to inhibit norepinephrine release or the reduced ability to inhibit renin activity. After 1 and 2 weeks of tachypacing, the basal norepinephrine-release rate in individual dogs varied 8.6-55.5 ng/kg/min and the basal renin activity varied 0.1-22.6 ng/ml/hr.…”

The heart is the center of a new endocrine, paracrine, and neuroendocrine system.

“…The stimulation of myoendocrine cells is also documented by the numerous exocytotic profiles which are detected during the functional state of an increased release of CDD-99-126 which may be followed by an increase in plasma CDD concentrations via radioimmunoassay. Chronic stimulation of myoendocrine cells may follow in pathological states of the human endocrine heart (SPATH et al, 1986) or after chronic cardiac pacing (RIEGGER et al, 1988). Here, a hypertrophy of the Golgi complex, an increase in telenuclear dictysomes, and an increase in the frequency of exocytotic events are observed.…”