[Endogenous natriuretic and ouabain-like factors. Their potential role in volume and blood pressure regulation].
The existence of an endogenous natriuretic hormone and ouabain-like factors (OLF) has been postulated for many years. This postulate was based on our original observation that a small M.W. fraction in the serum after acute expansion of the extracellular fluid volume (ECFV) not only exhibited natriuretic activity but also inhibited the Na-K-ATPase enzyme in vitro similar to ouabain. Since then, numerous studies confirmed the presence of OLFs in serum, urine, cerebrospinal fluid, and various organs including the heart and hypothalamus. Some of these OLFs are well-known endogenous compounds, such as free unsaturated fatty acids, which inhibit in vitro transmembranous sodium transport, Na-K-ATPase and 3H-ouabain binding to its membrane receptor or cross-react with digoxin antibodies. Chemically yet undefined OLFs of potentially hypothalamic origin were detected in various models of experimental and clinical hypertension and are suggested to play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs isolated from the urine of salt-loaded healthy subjects strongly enhance basal and vasopressin-stimulated release of calcium in vascular smooth muscle cells and platelets similar to the effects we had observed with endothelin. This urine fraction also exhibits natriuretic activity which increases in parallel with sodium intake. Further chromatographic separation and amino acid analysis confirmed the peptidic nature (M.W. less than 1000) of the natriuretic factor(s). However, the two biological activities, namely natriuretic and ouabain-like activities, reside in distinct and chemically different compounds.(ABSTRACT TRUNCATED AT 250 WORDS)
Kramer
H J
HJ
Medizinische Poliklinik, Universität Bonn.
Bäcker
A
A
Krampitz
G
G
Meyer-Lehnert
H
H
Michel
H
H
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002298:Cardenolides; D004077:Digoxin; D007424:Intracellular Fluid / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009318:Natriuresis; D010953:Plasma Volume / Q000187:drug effects*; D051381:Rats; D012503:Saponins; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology
D002298:Cardenolides; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; D009320:Atrial Natriuretic Factor; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium
Endogene Natriuretische und Ouabain-ähnliche Faktoren. Ihre potentielle Rolle bei der Volumen- und Blutdruckregulation.