Evidence for a Hormone other than Aldosterone which Controls Urinary Sodium Excretion

Endogenous Cardiotonic Steroids: Physiology, Pharmacology, and Novel Therapeutic Targets

“…Buckalew et al (1970) demonstrated that an ultrafiltrate of volume-expanded dogs inhibited sodium transport in toad bladders and postulated that this ultrafiltrate contained an inhibitor of the Na + /K + -ATPase. Extremely important contributions were made by Schrier and de Wardener in the measurement and implications of this factor (De Wardener et al, 1961; de Wardener et al, 1968, 1971; Schrier et al, 1968a,b; Schrier, 1974). Kramer and Gonick (1974) were later able to demonstrate that volume expansion in rats produced a substance that could inhibit ATPase activity in rat kidney.…”

Natriuretic Hormones in Brain Function

“…These compounds, originally discovered in plants and toad skin, have been used for centuries in Eastern and Western medicine to treat cardiac failure ( 136 ). Investigation into these substances started with the search for a missing “third factor” in the regulation of sodium homeostasis, as described in the classic work by de Wardener et al ( 137 ). Although the interest in endogenous CS as the “third factor” has subsided with the finding of the NH, these studies paved the way for the recognition of CS in mammalian tissues and circulation.…”

The Trade-Off between Dietary Salt and Cardiovascular Disease; A Role for Na/K-ATPase Signaling?

“…In 1980, Gruber and Buckalew noted that elevated levels of circulating digoxin-like material was seen in volume-expanded dogs ( 23 ). Other important contributions were made in the laboratory of Schrier and de Wardener over the next decade ( 24 – 26 ). However, doubt as to the validity of Na/K-ATPase inhibitors developed during the 1980s and 1990s because of inconsistencies in the reported results.…”