Effects of three sodium-potassium adenosine triphosphatase inhibitors.
Reports from several laboratories suggest the presence of an ouabainlike compound in plasma and various animal tissues, particularly during acute volume expansion and in low-renin hypertension. It has been hypothesized that this compound, through inhibition of the Na(+)-K+ pump, can constrict blood vessels, enhance vasoconstriction in response to agonists, increase cardiac contractility, raise blood pressure, and cause natriuresis/diuresis and therefore is implicated in the pathophysiology of the low-renin, volume-expanded type of hypertension. However, so far, only two steroid Na(+)-K+ pump inhibitors (namely, a bufodienolide derivative [resibufogenin], obtained from toad skin and plasma and a factor with the same carbon, oxygen, and hydrogen content as ouabain obtained from the plasma of volume-expanded humans) have been purified and structurally characterized. To determine whether such endogenous Na(+)-K+ pump inhibitors can in fact produce the above effects on the cardiovascular and renal systems, we infused commercially available bufalin (aglycone, identical to resibufogenin except for one H+), ouabain, and ouabagenin (aglycone) at equimolar doses in normotensive rats. Relative to ouabain, bufalin produced significantly greater dose-dependent increases in blood pressure, left ventricular rate of pressure change, heart rate, and excretion of urinary volume and sodium. Ouabagenin was without effect on any of these parameters. These data indicate that a Na(+)-K+ pump inhibitor can cause an increase in blood pressure despite potent diuretic and natriuretic effects and that, in rats, bufalin is much more potent in this respect than ouabain or ouabagenin.
Pamnani
M B
MB
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Chen
S
S
Bryant
H J
HJ
Schooley
J F
JF
Eliades
D C
DC
Yuan
C M
CM
Haddy
F J
FJ
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002018:Bufanolides / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010042:Ouabain / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*
D002018:Bufanolides; D000804:Angiotensin II; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; C008721:ouabagenin; D011188:Potassium; C022777:bufalin