The amino acid sequence of an atrial peptide with potent diuretic and natriuretic properties

THE SEARCH for natriuretic hormones or factors by studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibitors and parabiosis experiments in Dahl rats has led to the finding that the atria are a peptide-secreting endocrine gland. This new natriuretic hormone has now been purified, sequenced and synthetized, and its cDNA and gene have been cloned. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are beginning to emerge.

The Heart and the Atrial Natriuretic Factor

Mammalian atrial extracts possess natriuretic and diuretic activity. In experiments reported here it was found that atrial, but not ventricular, extract also causes relaxation of isolated vascular and nonvascular smooth muscle preparations. The smooth muscle relaxant activity of atrial extract was heat-stable and concentration-dependent and could be destroyed with protease. Rabbit aortic and chick rectum strips were used for the detection of atrial biological activity. The atrial activity was separated by column chromatography into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. The atrial substance that copurified with the smooth muscle relaxant activity in both peaks caused natriuresis when injected into conscious rats. It appears that atria possess at least two peptides that elicit smooth muscle relaxation and natriuresis, suggesting an endogenous system of fluid volume regulation.

https://science.sciencemag.org/content/sci/221/4605/71.full.pdf

Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria.

Studies were performed in anesthetized dogs (n = 5) to determine the effects of synthetic atrial natriuretic factor on renal function and renin release. Intrarenal infusion of synthetic atrial natriuretic factor (ANF) (0.3 microgram X kg-1 X min-1) resulted in a transient increase in renal blood flow (126 +/- 8 to 148 +/- 11 ml/min). The duration of this transient vasodilation was 3.1 +/- 0.4 min. Continued infusion was followed by a slight decrease in renal blood flow (126 +/- 8 to 117 +/- 8 ml/min) and an increase in glomerular filtration rate (23.1 +/- 3.5 to 30.7 +/- 1.9 ml/min), with filtration fraction thus being increased (0.19 +/- 0.04 to 0.27 +/- 0.03). These hemodynamic alterations were associated with increases in fractional sodium excretion (0.6 +/- 0.2 to 5.8 +/- 0.8%), fractional potassium excretion (30.8 +/- 9.4 to 56.3 +/- 7.4%), fractional lithium excretion (32.2 +/- 7.1 to 60.3 +/- 5.7%), and fractional phosphate excretion (8.7 +/- 3.5 to 41.6 +/- 11.7%). Intrarenal infusion of synthetic ANF markedly suppressed renin secretion rate (295.5 +/- 84.6 to 17.2 +/- 10.6 ng/min) despite a slight reduction in arterial pressure (123 +/- 9 to 118 +/- 9 mmHg). Our studies demonstrate that synthetic ANF results in a marked natriuretic response that is in part mediated by an increase in glomerular filtration rate. The increase in fractional lithium and phosphate excretion suggests that this factor may also have an action on proximal tubule reabsorption. Further, these studies demonstrate that synthetic ANF markedly inhibits renin secretion.

https://www.physiology.org/doi/pdf/10.1152/ajprenal.1984.247.5.F863

Effects of synthetic atrial natriuretic factor on renal function and renin release

https://www.amjmed.com/article/0002-9343(84)90190-6/pdf

Effects of auriculin (atrial natriuretic factor) on blood pressure, renal function, and the renin-aldosterone system in dogs

In anesthetized rats micropuncture and microcatheterization were used to collect tubular fluid from end proximal and distal tubules and from the outer medullary collecting duct. Urine was collected at the papilla tip. Samples were taken from the same sites before and after intravenous injection of atrial tissue extract; rats injected with ventricular extract served as controls. Sodium excretion increased 17-fold after atrial extract, a significantly greater rise than the 3-fold increase after ventricular extract. Clearances of inulin and single nephron filtration rates did not change significantly in either group. Tubular fluid collection results showed a similar reduction (16 to 20%) of proximal fluid and sodium reabsorption in both groups. In the experimental group only, NaCl reabsorption failed to rise in response to increased load in the medullary collecting duct. The resulting fall in fractional reabsorption in the medullary collecting duct accounted for 80% of the natriuresis. We conclude that atria...

Intrarenal localization of the natriuretic effect of cardiac atrial extract.

1. An extract of cardiac atrial tissue, when injected intravenously into anaesthetized rats, caused a large and rapid increase in renal excretion of sodium chloride. 2. The renal response to atrial extract was associated with increases in total and medullary blood flow in the kidney, as measured by microsphere and albumin uptake methods, respectively. 3. The data suggest that these changes in renal haemodynamics may contribute to, but are unlikely to be the complete cause of, the natriuresis and chloriuresis following injection of atrial tissue extract.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/jphysiol.1983.sp014484

The effect of a natriuretic atrial extract on renal haemodynamics and urinary excretion in anaesthetized rats.

In anesthetized rats micropuncture and microcatheterization were used to collect tubular fluid from end proximal and distal tubules and from the outer medullary collecting duct. Urine was collected at the papilla tip. Samples were taken from the same sites before and after intravenous injection of atrial tissue extract; rats injected with ventricular extract served as controls. Sodium excretion increased 17-fold after atrial extract, a significantly greater rise than the 3-fold increase after ventricular extract. Clearances of inulin and single nephron filtration rates did not change significantly in either group. Tubular fluid collection results showed a similar reduction (16 to 20%) of proximal fluid and sodium reabsorption in both groups. In the experimental group only, NaCl reabsorption failed to rise in response to increased load in the medullary collecting duct. The resulting fall in fractional reabsorption in the medullary collecting duct accounted for 80% of the natriuresis. We conclude that atrial tissue from rat hearts contains a factor which causes increased renal NaCl excretion by inhibiting transport in the medullary collecting duct.

Intrarenal Localization of the Natriuretic Effect of Cardiac Atrial Extract

Fifteen-micrometer microspheres were used to study renal blood flow in rats which had been cannulated 3 or more days previously. Renal blood flow was assessed while the animals were conscious, afte...

W. A. Cupples

Papers

Intrarenal localization of the natriuretic effect of cardiac atrial extract.

The effect of a natriuretic atrial extract on renal haemodynamics and urinary excretion in anaesthetized rats.

Intrarenal Localization of the Natriuretic Effect of Cardiac Atrial Extract

Lack of effect of barbiturate and ketamine anesthesia on renal blood flow in chronically instrumented rats prepared for micropuncture