Effects of an endogenous ouabainlike compound on heart and aorta

Abstract

An endogenous ouabainlike compound (OLC) has been purified from human plasma, and mass spectrometry has shown it to be indistinguishable from plant-derived ouabain. This human OLC was tested for its effects on evoked tension in guinea pig left atria and aortic rings. The tissues were incubated at 37°C in bicarbonate-buffered physiological salt solution gassed with 95% O2-5% CO2. In atria stimulated electrically at 1 Hz, 85 and 170 nM human OLC increased peak active force to 177±15% and 313±32% of control, respectively (n=3), with little effect on the duration of contraction. On washout of the OLC, peak systolic force returned to the control level with a half-time of 4.3±0.5 minutes. Similar results were obtained with 160 nM plant-derived ouabain: peak systolic force increased to 310±31% of control (n=4) and returned to the control level with a half-time of 3.8±0.2 minutes during washout. In aortic rings, neither 170 nM human OLC nor 160 nM plant ouabain (30-minute treatments) affected resting (unstimulated) tension, but they increased the contractions evoked by histamine (0.2-1.0 μM) to 156±13% (n=4) and 143±6% (n=4) of control responses, respectively. The mean half-time for washout of the OLC and plant ouabain-induced augmentation of histamine-evoked tension exceeded 35 minutes. These data show that human OLC has cardiotonic and vasotonic actions qualitatively and quantitatively similar to those observed with plant ouabain. Together with data on the mass spectrometry, chromatographic characteristics and interaction with Na+,K+-ATPase, and full cross-reactivity with polyclonal anti-ouabain antibodies, these physiological findings support the view that human OLC is ouabain.