Role of the ouabain-like factor and Na-K pump in rat and human genetic hypertension.
Endogenous ouabain-like factor (OLF) is present in mammal tissues and after standardized extraction procedure can be similarly quantified by two independent assays: RIA and Na-KATPase inhibition. OLF was quantified both from plasma and tissues obtained from MHS hypertensive and MNS normotensive rats, maintained under the same environmental and dietary conditions, and from plasma of healthy volunteers and essential hypertensive patients. OLF biochemical characterization shows that it behaves like ouabain except for a 1000-fold higher affinity for the ouabain low-affinity Na-KATPase isoforms than ouabain. Tissue and plasma levels of OLF are higher in MHS than in MNS rats and are not influenced by exogenous OLF sources. Plasma OLF is also increased in a subgroup of hypertensive patients. Both in rats and humans a primary cell membrane alteration affecting ion transports seems to be linked to the increased levels of OLF. An antihypertensive compound which selectively antagonizes the pressor effect of OLF and corrects the ion transport defect is under development and can represent a new pharmacological approach to the treatment of hypertension.
PRASSIS-Sigma Tau Research Institute, Settimo Milanese, Milan, Italy.
M
M
Ferrandi
P
P
Manunta
R
R
Rivera
G
G
Bianchi
P
P
Ferrari
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001685:Biological Factors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D002298:Cardenolides; D002851:Chromatography, High Pressure Liquid; D004077:Digoxin; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR; D012503:Saponins; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001685:Biological Factors; D002298:Cardenolides; D004791:Enzyme Inhibitors; D012503:Saponins; C034504:digoxin-like factors; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase