Pulse pressure correlates in humans with a proscillaridin A immunoreactive compound

Area of Science:

• Cardiovascular Physiology
• Endocrinology
• Biochemistry

Background:

• Endogenous digitalis-like factors, including cardenolides and bufadienolides, are suspected to play physiological roles in humans.
• The presence and function of bufadienolide-like substances in human circulation remain largely uncharacterized.

Purpose of the Study:

• To investigate the existence of bufadienolide-like substances in human blood.
• To quantify these substances and assess their correlation with blood pressure parameters.

Main Methods:

• Utilized rabbit antibodies against bufadienolide proscillaridin A for an indirect enzyme-linked immunosorbent assay (ELISA) to detect cross-reacting material in human plasma.
• Employed ethanol extraction and high-performance liquid chromatography (HPLC) for isolation and purification of plasma components.
• Assessed the inhibitory effect of isolated fractions on the sodium pump of human red blood cells.

Main Results:

• Identified three hydrophobic fractions (ED1, ED2, ED3) in human plasma that cross-reacted with proscillaridin A antibodies and inhibited the sodium pump.
• The concentration of ED1 in normotensive subjects showed a geometric mean of 0.1 nmol/L.
• ED1 levels positively correlated with mean arterial pressure, systolic pressure, and pulse pressure in normotensive subjects and patients with hypertension or chronic renal failure.

Conclusions:

• Multiple bufadienolide-like substances, detectable by proscillaridin A antibodies, circulate in human blood.
• These endogenous compounds inhibit the sodium pump, indicating potential physiological relevance.
• The concentration of ED1 is linked to blood pressure, suggesting a role in cardiovascular regulation.