Pulse pressure correlates in humans with a proscillaridin A immunoreactive compound.
Endogenous digitalis-like factors in humans are presumably cardenolides and bufadienolides. To test whether bufadienolide-like substances may circulate in human blood, we used antibodies from rabbits against the bufadienolide proscillaridin A to measure the concentration of cross-reacting material in human plasma with an indirect enzyme-linked immunosorbent assay. IgG had an apparent affinity of 2 x 10(-9) mol/L for proscillaridin A. It was specific for bufadienolides and did not cross-react with cardenolides or several steroid hormones. Extraction of human plasma with ethanol and fractionation of this extract over a high-performance liquid chromatographic reverse-phase C18 column with a propanol/isopropanol gradient resulted in the separation of three peaks of increasing hydrophobicity (ED1, ED2, ED3) that inhibited the sodium pump of human red blood cells and cross-reacted with proscillaridin A antibodies. The concentration of the proscillaridin A immunoreactivity ED1 in normotensive subjects had a geometric mean of 0.1 nmol/L, with a dispersion factor of 8.77. ED1 correlated positively in a group of 60 normotensive subjects, 22 patients with hypertension, and 19 patients with chronic renal failure with mean arterial blood pressure (log ED1 [nmol/L] = 0.013 x mm Hg-2.17, r = .25, P < .05), systolic pressure (log ED1 [nmol/L] = 0.010 x mm Hg-2.23, r = .32, P < .01), and pulse pressure (log ED1 [nmol/L] = 0.019 x mm Hg-1.80, r = .38, P < .0001). There was no correlation with other parameters of the donors. We conclude that several substances cross-reacting with proscillaridin A antibodies and inhibiting the sodium pump of human red blood cells circulate in human blood. The level of one of these substances (ED1) correlates with mean arterial and pulse pressures.
Sich
B
B
Institut für Biochemie und Endokrinologie, Justus-Liebig-Universität Giessen, Germany.
Kirch
U
U
Tepel
M
M
Zidek
W
W
Schoner
W
W
D000328:Adult; D000818:Animals; D001794:Blood Pressure; D002018:Bufanolides; D002770:Cholenes / Q000276:immunology; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000276:immunology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011442:Proscillaridin / Q000276:immunology*; D011817:Rabbits; D012016:Reference Values; D013599:Systole
D002018:Bufanolides; D002770:Cholenes; C087925:bufadienolide; D011442:Proscillaridin