R. S. Zimmerman

Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor.

The current studies were designed to investigate the mechanisms in the intact anesthetized dog that control the release of atrial natriuretic factor (ANF). In vitro, mechanical stretch of atrial tissue produces an increased release of ANF. In vivo, changes in atrial pressure correlate positively with circulating ANF levels. The present investigations used 6 open-chest anesthetized dogs to evaluate the role of atrial pressure versus atrial stretch, the latter determined by atrial transmural pressure, in the release of ANF. In a paired design, animals underwent cardiac tamponade followed by constriction of the aorta and pulmonary artery. Tamponade produces a balanced increase in intra-atrial and pericardial pressures. Thus, despite an elevated atrial pressure, there is no increase in transmural pressure producing atrial stretch. Great artery constriction increases intra-atrial but not pericardial pressure, resulting in an increase in atrial transmural pressure and atrial stretch. Cardiac tamponade increased right atrial pressure (0.8 +/- 0.3 to G.6 +/- 0.6 mm Hg, p less than 0.001) and pulmonary capillary wedge pressure (3.7 +/- 0.6 to 8.8 +/- 0.6 mm Hg, P less than 0.001). Constriction of the aorta and pulmonary artery also increased right atrial pressure (1.5 +/- 0.8 to 6.3 +/- 0.8 mm Hg, p less than 0.05) and pulmonary capillary wedge pressure (4.6 +/- 0.3 to 7.8 +/- 1.0 mm Hg, p less than 0.05). Atrial transmural pressure increased only during great artery constriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardio-renal-endocrine dynamics during stepwise infusion of physiologic and pharmacologic concentrations of atrial natriuretic factor in the dog.

Infusion of alpha-human atrial natriuretic factor (alpha-h-ANF) into pentobarbital anesthetized dogs (n = 10) at 0.0025, 0.005, 0.01, and 0.3 micrograms/kg/min was performed to differentiate the physiologic actions of atrial natriuretic factor from its pharmacologic actions. The lowest doses of atrial natriuretic factor infusion resulted in circulating levels that were previously produced by 0-10% saline volume expansion. At the lowest infusion rate, circulating ANF increased 31 +/- 3 pg/ml, resulting in a significant increase in absolute sodium excretion, fractional excretion of sodium, and fractional excretion of lithium, and a significant decrease in urine osmolality. A greater change in circulating atrial natriuretic factor (96 +/- 12 pg/ml) was required to significantly decrease right atrial pressure, cardiac output, and plasma renin activity, and to increase systemic vascular resistance and total and fractional excretion of potassium. The highest dose of atrial natriuretic factor infused was required to decrease arterial pressure and renal vascular resistance. The present study demonstrates that atrial natriuretic factor is natriuretic and diuretic at physiologic concentrations; at low concentrations, atrial natriuretic factor appears to decrease the whole kidney proximal tubular reabsorption of sodium and does not affect glomerular filtration rate; a greater (but physiologic) change in circulating atrial natriuretic factor is required to significantly decrease cardiac output, cardiac filling pressure, and plasma renin activity than is required to significantly increase sodium excretion; and a decrease in systemic arterial pressure and vascular resistance does not occur at physiologic concentrations of atrial natriuretic factor.

Atrial natriuretic peptide decreases cardiac output independent of coronary vasoconstriction

Abstract Studies were performed in isolated, Langendorff-perfused rat hearts and anesthetized dogs to determine the effects of synthetic atrial natriuretic peptide (ANP 8-33) on the coronary circulation. In vitro studies in the rat examined coronary flow dynamics to ANP 8-33 over a defined range from physiologic to pharmacologic concentrations. No changes in coronary flow or chronotropic and inotropic function of the isolated Langendorff-perfused heart were observed in response to increasing concentrations of ANP 8-33 (102 to 106 pg/ml). In the dog, a low, nonhypotensive dose of ANP 8-33 (0.05 μg/kg/min) decreased cardiac output with no change in coronary blood flow or coronary vascular resistance. At a high, hypotensive dose (0.3 μg/kg/min) ANP 8-33 decreased cardiac output in association with transient coronary vasodilation. Continued infusion resulted in a decrease in coronary blood flow and arterial pressure with no change in coronary vascular resistance. Thus, in vitro physiologic and pharmacologic concentrations of ANP, or in vivo low concentrations of ANP, do not result in an alteration in coronary flow. In vivo ANP 8-33, at both nonhypotensive and hypotensive concentrations, decreased cardiac output in the absence of coronary vasoconstriction.

Atrial natriuretic factor: physiologic actions and implications in congestive heart failure.

SummaryAtrial natriuretic factor (ANF) represents a newly recognized hormone of cardiac origin. This peptide is synthesized by the myocardial cells of both atria and released by atrial stretch. The hormone promotes sodium and water excretion by the kidney, inhibits the renin-angiotensin-aldosterone system, and reduces systemic arterial pressure. Specific receptors for ANF are present in the kidney, adrenal glands, vascular smooth muscle, platelets and central nervous system. Congrestive heart failure is characterized by increased circulating levels of ANF; however, there appears to be an attenuation in the renal response to the hormone.Recent investigations have reported the effect of systemic administration of synthetic ANF to normal individuals and those with congestive heart failure. The hormone may promote a significant natriuresis and diuresis in addition to reducing arterial pressure and inhibiting renin and aldosterone secretion. Substantial questions remain as to the full physiologic significance and therapeutic potential of this hormone.

Renal-endocrine adaptations to endogenous atrial natriuretic factor during tachycardia-induced reductions in renal perfusion pressure.

Atrial pressure, atrial natriuretic factor (ANF), the renin-angiotensin-aldosterone system, and renal hemodynamic functions were examined during and after right ventricular pacing in anesthetized dogs (n = 9). Mean arterial pressure, cardiac output, and renal blood flow decreased during tachycardia while right and left atrial pressures increased. ANF markedly increased during tachycardia but urinary and fractional excretion of sodium were unchanged from control. Plasma renin activity was not increased during pacing despite the decrease in renal perfusion pressure. After tachycardia and restoration of mean arterial pressure to control, ANF declined but remained elevated above control despite a return of atrial pressure to control level. After tachycardia, urinary and fractional sodium excretion increased significantly in the absence of an increase in glomerular filtration rate. These findings support the following conclusions: 1) tachycardia increases ANF in association with increased atrial pressure; however, an elevation of ANF persists following tachycardia despite the absence of the persistent stimulus of elevated atrial pressures; 2) the increase in ANF during tachycardia may contribute to the absence of a decrease in sodium excretion and activation of the renin-angiotensin system that occurs with reduction in renal perfusion pressure; and 3) tachycardia-induced natriuresis may be dependent on an increase in ANF and the maintenance of renal perfusion pressure.