ENDOGENOUS MARINOBUFAGENIN-LIKE IMMUNOREACTIVE SUBSTANCE - A POSSIBLEENDOGENOUS NA,K-ATPASE INHIBITOR WITH VASOCONSTRICTOR ACTIVITY

Vasoconstrictor and Na/K pump inhibitory properties of a bufodienolide Na/K-ATPase inhibitor, marinobufagenin, were studied in isolated ring s of 2 to 3 order branches of human pulmonary arteries respectively. M arinobufagenin displayed concentration-dependent vasoconstrictor activ ity (0.01 to 10 mmol/L). In sarcolemma membranes prepared from pulmona ry artery marinobufagenin inhibited Na/K-ATPase (IC50=50 nmol/L). In e ight healthy male Caucasians, concentrations of marinobufagenin-like i mmunoreactive material in C-18 extracted plasma were 1.38 10.60 nmol/L . Twenty-four-hour urinary release of marinobufagenin-like immunoreact ive material in eight healthy males was 1.20+/-0.95 nmol/day. Chlorofo rm extract of human urine was fractionated using reverse-phase high-pe rformance liquid chromatography (32% acetonitrile, Deltapak). The HPLC fraction coeluting with marinobufagenin in 7 min, cross reacted with antimarinobufagenin and antidigoxin, but not antiouabain antibody. The se results demonstrate that human plasma and urine contains a bufodien olide vasoconstrictor EDLF, marinobufagenin-like immunoreactive Na,K p ump inhibitor.