Evidence that the Brain Participates in the Humoral Natriuretic Mechanism of Blood Volume Expansion in the Dog

Decrease in Na+,K+-ATPase activity and [3H]ouabain binding sites in sarcolemma prepared from hearts of spontaneously hypertensive rats.

“…In our experiments, the K D value for the higher affinity site, as determined by a 35 originally proposed a relationship between a putative natriuretic hormone, perhaps secreted from the brain 36 and salt-related renal hypertension. 36 " 38 It has been suggested, e.g., that inhibition of the ouabain-sensitive Na + ,K + pump of smooth muscle membrane in salt-loaded or renal hypertensive animals is caused by circulation of this hormone in the plasma. Blaustein 37 concluded that a putative natriuretic hormone may play an important role in the development of hypertension and might act as the body's "endogenous digitalis."…”

Sodium transport inhibitor from bovine hypothalamus.

“…Assays in vitro of plasma and urine extracts from subjects and animals with expanded extracellular fluid volume (5,6), certain chronic uremic patients (7), and animals in mineralocorticoid "escape" (8) confirmed the biological effect of sodium transport inhibition across living cell membranes. Several investigators (9)(10)(11) have provided experimental evidence supporting the view that the brain is the source of the natriuretic factor(s). Despite the substantial indirect evidence for a circulating natriuretic substance, its precise chemical nature, source of production, and mechanism of action have remained obscure.…”

Partial Purification and Properties of the Inhibitors of Na,K‐ATPase and Ouabain‐Binding in Bovine Central Nervous System

“…Although the physiological role of these activities remains uncertain at present, it is likely that they relate to natriuresis (De Wardener, 1982). Furthermore, as suggested by many investigators (Kaloyanides et al, 1978;Fishman, 1979;Haupert and Sancho, 1979) it is possible that these inhibitors are secreted from the CNS to the blood stream, where they regulate the activity of Na,K-ATPase and sodium transport throughout the body as well as the renal function. Recently, a possible correlation between essential hypertension, a disorder of sodium metabolism, and the presence of Na,K-ATPase inhibitor in patients' plasma was suggested (Hamlyn et al, 1982) which seems to support this hypothesis.…”

“…Whether or not similar substances that are of importance physiologically are present in mammalian tissue is unclear. Recently, several attempts have been made to identify a sodium transport inhibitor, called "natriuretic factor," which is present in circulating plasma and can affect renal sodium excretion (Kaloyanides et al, 1978;Gruber and Buckalew, 1978; Raghavan and Gonick, 1980). Preliminary purification of natriuretic factors has shown the presence of low-molecular-weight substance(s) in CNS which could inhibit Na,K-ATPase and ouabain-binding (Fishman, 1979;Haupert and Sancho, 1979; Lichstein and Samuelov, 1980).…”