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(Hypertension. 1996;27:1073-1078.)
© 1996 American Heart Association, Inc.

Articles

Pulse Pressure Correlates in Humans With a Proscillaridin A Immunoreactive Compound

Beate Sich; Ulrike Kirch; Martin Tepel; Walter Zidek; Wilhelm Schoner

From the Institut für Biochemie und Endokrinologie, Justus-Liebig-Universität Giessen (B.S., U.K., W.S.), and Medizinische Poliklinik Münster, Westfälische Wilhelms-Universität Münster (M.T., W.Z.) (Germany).

Abstract 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 2x10^-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]=0.013xmm Hg-2.17, r=.25, P<.05), systolic pressure (log ED₁ [nmol/L]=0.010xmm Hg-2.23, r=.32, P<.01), and pulse pressure (log ED₁ [nmol/L]=0.019xmm 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.

Key Words: proscillaridin A • hypertension, essential • blood pressure • bufanolides • immunoassay • pulse pressure • Na⁺-K⁺-exchanging ATPase

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