Conversion of plasma noradrenaline from conjugated form into free form in the heart and its physiological significance in patients with cardiac diseases - a comparison between at rest and during exercise

To investigate the site of deconjugation of plasma conjugated noradrenaline (NA), we measured plasma levels of free and conjugated NA in the coronary sinus and the aorta simultaneously at rest and during dynamic leg exercise in patients with cardiac disease. Coronary sinus blood flow was also measured by a thermodilution method using a Webster catheter. NA overflow rate from the heart was calculated according to the following formula. NA overflow rate=[(plasma NA level in the coronary sinus - plasma NA level in the aorta) x coronary sinus flow x (100-Ht)/100]. We further examined if arylsulfatase can deconjugate the conjugated NA into free form in a short duration such as 2, 4 or 6 min, in a glass bottle suspended in a water bath at 37°C under condition of physiological pH or lower pH. Plasma free NA overflow rate from the heart at rest was 3.08±0.40 ng/min. Plasma conjugated NA overflow rate from the heart was -5.27±1.52 ng/min, the negative sign indicating an uptake. Dynamic leg exercise increased plasma free NA overflow rate from 2.75+0.45 ng/min to 6.21±1.31 ng/min and decreased plasma conjugated NA overflow rate from -4.38±1.84 ng/min to -8.83±2.47 ng/min, an increased uptake. Under condition of physiological pH, the addition of 1 mg of arylsulfatase led to a significant increase in plasma levels of free noradrenaline and led to a significant decrease in plasma levels of conjugated noradrenaline The additionl of 0.1 mg of arylsufatase did not affect plasma levels of free or conjugated noradrenaline. However, under condition of acidic pH, 0.1 mg of arylsulfatase led to a significant increase in plasma levels of free noradrenaline and to a significant decrease in plasma levels of conjugated noradrenaline These results suggest that, in man, plasma conjugated noradrenaline can be deconjugated into plasma free noradrenaline, at least in part, in the coronary circulation where there is an abundance of arysulfatase that hydrolyzes the conjugated to the free noradrenaline, and that the deconjugation is accelerated probably due to acidic change in pH in the myocardium during dynamic leg exercise.