Effect of Atrial Extract on Renal Function in the Rat

Abstract

1. The effects of myocardial extracts on renal function were studied in the rat. Infusion of rat atrial extract but not of ventricular extract resulted in a significant natriuresis in both pentobarbitone anaesthetized and unanaesthetized rats that were either deprived of food and water (for 18 h before the experiment) or were expanded with isotonic sodium chloride solution (1.5% body weight/h) during the experiment. 2. The increase in sodium excretion was three to four times greater in both groups of volume-expanded rats than in the two groups of food- and water-deprived rats. 3. Glomerular filtration rate and renal blood flow were not affected by atrial extract, indicating that the atrial natriuretic factor (ANF) directly inhibited sodium reabsorption at the tubular level. 4. Distal tubular blockade with a combination of frusemide and amiloride was employed to differentiate between proximal and distal tubular sites of action of ANF. Infusion of atrial extract into saline-expanded, distally blocked rats resulted in a transient increase in both the glomerular filtration rate and sodium excretion; fractional sodium excretion was unaffected by atrial extract in these experiments. 5. We conclude that (a) the renal response to ANF is not affected by pentobarbitone anaesthesia, (b) the renal response to ANF is dependent on the state of the extracellular fluid volume of the animal and (c) that ANF inhibits sodium reabsorption in the distal nephron.

Blood levels and renal effects of atrial natriuretic peptide in normal man.

“…A similar trend has been noted in the anesthetized dog or rabbit (21,46), although consistent decreases (22), unchanged values (16,18,23,24), or even dosedependent increases (1,25,26) in total renal blood flow were noted in other animal experiments, some of which were based on injection ofrather than constant infusion ofANP. Increasing the ahANP infusion rate from 6.25 to 12.5 ,ug/min in the normal subjects was accompanied by a greater fall in ERPF.…”

“…However, while GFR was apparently unaltered in the unsteady state after single-dose injection (1,(15)(16)(17)(18), distinct increases in GFR and, thus, filtered loads ofsodium, were noted during a constant infusion of rat atrial extract or synthetic ANP in the isolated kidney (19,20) and in some (21)(22)(23), but not all (24), studies in the intact rat or dog. On the other hand, total renal blood flow was variably reported as increased (20,25,26), unchanged (16,(22)(23)(24), or after an initial rise, even decreased (21).…”

Renal mechanism of action of rat atrial natriuretic factor.

“…Other groups have suggested that the renal effect is not mediated by a change in GFR (1, 9-16) but rather by redistribution of blood flow (10) or by direct inhibition of proximal reabsorption (11), of loop reabsorption (10,12), or of collecting duct reabsorption (13)(14)(15)(16). Difficulties with these studies include: (a) use of crude, unpurified extracts of the right atrium (1,6,7,(9)(10)(11)(12)(13)(14)(15)(16)) that may contain contaminants with vasodilatory but not natriuretic properties (17); (b) use of volume contracted animals (10,14,15); (c) use of isolated renal membrane vesicles without correlation to in vivo effects ( 11); (d) use of an in vitro isolated perfused kidney preparation with impaired base-line hemodynamics (4,6); and (e) unstable time controls (14). To date, there have been no micropuncture investigations examining the renal mechanism of action of ANF using a pure peptide in animals in a euvolemic state.…”

“…Within the last few years, a vasodilatory, natriuretic compound derived from granules within cardiocytes of the right atrium has been described (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). This substance has been very recently characterized as a closely related group of peptides of 21-26 amino acids (2-4) derived from a common precursor polypeptide of 152 amino acids (3,5).…”

The effects of intravenous injection of .ALPHA.-human atrial natriuretic polypeptide on blood pressure, renal hemodynamics and urinary kinin excretion in anesthetized rabbits.

“…Some studies have suggested an increase in renal blood flow (Keeler and Azzarolo 1983;Vaughan et al 1983), and others have indicated no effect on renal blood flow (Keeler 1982;Pollock and Banks 1983;Beasley and Malvin 1985). These conflicts of the mechanism of action of atrial extract include use of crude, unpurified extracts of the right atrium that may contain contaminants.…”