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 noradren aline (NA), we measured plasma levels of free and conjugated NA in the coronary sinus and the aorta simultaneously at rest and during dynami c leg exercise in patients with cardiac disease. Coronary sinus blood flow was also measured by a thermodilution method using a Webster cath eter. 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 conj ugated 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 degrees C under condit ion 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 overfl ow rate from the heart was -5.27+/-1.52 ng/min, the negative sign indi cating an uptake. Dynamic leg exercise increased plasma free NA overfl ow rate from 2.75+/-0.45 ng/min to 6.21+/-1.31 ng/min and decreased pl asma 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 addition of 0.1 mg of arylsulfatase did not affect plasma levels of free or conjugated no radrenaline. However, under condition of acidic pH, 0.1 mg of arylsulf atase led to a significant increase in plasma levels of free noradrena line and to a significant decrease in plasma levels of conjugated nora drenaline. These results suggest that, in man, plasma conjugated norad renaline can be deconjugated into plasma free noradrenaline, at least in part, in the coronary circulation where there is an abundance of ar ylsulfatase that hydrolyzes the conjugated to the free noradrenaline, and that the deconjugation is accelerated probably due to acidic chang e in pH in the myocardium during dynamic leg exercise.