Intravenous injection of a saline extract of lyophilized rat atrial myocardium into anesthetized rats caused a massive diuresis and natriuresis of short duration. There was also a significant increase in potassium excretion and a fall in urine osmolality. There were no significant changes in solute-free water reabsorption, glomerular filtration rate, renal plasma flow, or filtration fraction as measured by conventional clearance methods. Mean arterial pressure was significantly reduced during the natriuretic response. The natriuretic and diuretic response was not blocked by inhibition of prostaglandin synthesis with aspirin and indomethacin. Infusion of a small amount of atrial extract directly into the left kidney resulted in a natriuretic and diuretic response which was predominantly localized to the left kidney. It is concluded that saline extracts of rat atrial myocardium contain a potent natriuretic substance which acts directly on kidneys by a mechanism which does not depend upon increased synthesis of prostaglandins.

The intravenous injection of an extract of atrial myocardium into anesthetized rats during a hypotonic diuresis resulted in an increase in the renal excretion of water, sodium, potassium, calcium, magnesium, and phosphate. There was an increase in urine concentration which was probably a result of the secretion of vasopressin since it did not occur in Brattleboro (di/di) rats. A transient increase in glomerular filtration rate and renal plasma flow occurred during the first five minutes with a more sustained rise in filtration fraction. Injection of atrial extract also caused a partial inhibition of solute-free water formation in Brattleboro rats subjected to water diuresis and a partial inhibition of solute-free water reabsorption in rats subjected to maximal antidiuresis by infusing vasopressin. In neither case was the degree of inhibition as profound as that observed after injecting furosemide in a dose which caused a comparable natriuretic response. A large dose of furosemide blocked the natriuretic response to atrial extracts whereas, when a comparable level of sodium and water output was produced by massive infusions of saline, the natriuretic response to atrial extract was increased. It is suggested that atrial natriuretic factor might inhibit sodium transport in nephron segments beyond the medullary thick ascending limb. Furosemide might also act at the same tubular site or inhibit tubular secretion of the atrial natriuretic factor.

Immunoreactive atrial natriuretic peptide (iANP) levels in plasma of edematous rats with an experimental nephrotic syndrome produced by the injection of puromycin aminonucleoside (PAN) were not different from those in untreated rats. To test the ability of nephrotic rats to secrete iANP in response to a volume stress, the rats were subjected to 20% expansion of their estimated blood volumes using blood from donor rats. PAN-treated rats had very small natriuretic and diuretic responses compared with untreated rats; however, there was no difference in the secretory response of iANP, which increased approximately threefold in each group. There were highly significant correlations between changes in plasma iANP and changes in right atrial pressure in both normal and nephrotic rats. Nephrotic rats that were infused with synthetic ANP showed only a very small natriuretic and diuretic response compared with normal rats, and no change in glomerular filtration rate. The hypotensive response was still present, however. Urine concentration in nephrotic rats was much lower than in controls and was not increased by exogenous arginine vasopressin. It is concluded that the absence of a normal natriuretic and diuretic response to hypervolemia in PAN-treated rats is not caused by a failure to secrete ANP but might be a result of an intrarenal defect that makes their kidneys unresponsive.

Injection of salmon calcitonin into rats caused a significant increase in the excretion of sodium and water in a dose as small as 4 × 10−9 g. There appeared to be a linear relationship between sodium excretion and the log dose of calcitonin. Potassium excretion and free-water clearance were not significantly affected. Thyroparathyroidectomized rats showed no impairment in their ability to excrete sodium either before or after saline loading.

The time course of changes in the plasma concentration of immunoreactive atrial natriuretic peptide (iANP) accompanying tachycardia was measured in anesthetized rabbits. In contrast to the hemodynamic changes, which occurred within the 1st min of tachycardia, the plasma iANP increased gradually and did not reach significantly elevated levels until 10 min into the stimulation period. After 20 min of tachycardia iANP was almost 200 pg/ml. Immunoreactive ANP was measured prior to and following extraction. Although the basal levels of iANP were higher in the unextracted than in extracted plasma (62 vs. 22 pg/ml), the time course of changes in iANP was identical in both. The gradual increase in iANP suggests that the release of iANP in this model may not simply be a consequence of the increase in atrial pressure.

Atrial natriuretic peptide (ANP) was measured in plasma of dogs and rabbits by radioimmunoassay (RIA) using a commercially available anti alpha-ANP serum and compared to our measurements of ANP in rats and humans. Plasma concentration of ANP in dog coronary sinus (234.9 +/- 41.0 pg/ml) was significantly greater than in systemic arterial blood (81.2 +/- 8.4 pg/ml). Gel filtration of dog coronary sinus plasma resulted in an ANP peak with the elution volume (Ve) of synthetic atriopeptin III (AIII) and a minor peak eluting with the void volume (Vo). Rabbit systemic arterial plasma ANP was 53.3 +/- 4.3 pg/ml and yielded one peak, with a Ve of AIII. Ion exchange chromatography of dog and rabbit atrial extracts (AE) resulted in a major ANP region which resembled AIII. Gel filtration of AE showed larger molecular species as well as AIII. Dilutions of dog and rabbit plasma and AE were parallel with the AIII standard in radioimmunoassay.

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The injection or infusion of NIAMDD prolactin (NIH P-S-10) into unanesthetized rats resulted in water and electrolyte retention with a large increase in urine osmolality but no effect on glomerular filtration rate. Since these effects on urine output were also observed in homozygous Brattleboro rats, the antidiuretic activity could not have caused by the release of endogenous antidiuretic hormone. Radioimmunoassay of NIH prolactin showed that it was contaminated with vasopressin (20 ng/mg of prolactin). By comparison, Sigma prolactin had no observed effect on urine excretion and contained very little vasopressin (2.5 ng/mg). It is concluded that some of the renal effects of prolactin have been reported in the literature may have been caused by the contaminating vasopressin.