Role of ouabain-like factors in hypertension: effects of ouabain and certain endogenous ouabain-like factors in hypertension.
Several reports suggest the presence of sodium-potassium pump inhibitor in plasma and various tissues, particularly during volume-expanded state and low-renin hypertension. It has been hypothesized that by inhibiting the cardiovascular muscle-cell Na(+)-K+ pump, this inhibitor can constrict blood vessels, enhance vasoconstriction, and increase cardiac contractility, thereby raising blood pressure. Only two such endogenous inhibitors have been chemically characterized: the bufodienolide derivative, resibufogenin, obtained from toad skin and plasma; and a factor with the same structure (based on mass spectral analysis) as ouabain, from human plasma. However, unlike bufalin (aglycone), which is almost structurally identical to resibufogenin, neither ouabain nor ouabagenin (aglycone of ouabain) caused a sustained increase in blood pressure when infused in equimolar doses during a 30-min period in rats. Because the rat is 10(4)-fold less sensitive to ouabain than the human is, we wondered whether the absence of a response to ouabain was due to the short infusion time. Therefore, in new experiments ouabain was administered chronically during a 6- to 7-week period to two-kidney normal rats and rats with 70, 60, and 25% reduced renal mass. Reduced renal mass rats were used because these rats have decreased sodium excretion capacity, and thus we hoped the action of exogenous ouabain would be potentiated in these volume-expanded rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Yuan
C
C
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Manunta
P
P
Chen
S
S
Hamlyn
J M
JM
Haddy
F J
FJ
Pamnani
M B
MB
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010042:Ouabain / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects
D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase