Exercise Reduces Production of Endothelin in the Coronary Circulation

We have previously shown that withdrawal of an endothelin (ET)‐mediated vasoconstrictor influence during exercise contributes to metabolic vasodilation of the porcine coronary vasculature. The aim of the present study was to investigate if this reduced ET‐mediated vasoconstriction during exercise was due to a reduced production of ET from its precursor Big‐Endothelin (BigET) and/ or a reduced sensitivity of the coronary vasculature to ET.Changes in coronary blood flow (CBF) and coronary venous oxygen pressure (cvPO2) in response to graded infusions of ET (10 and 20 pmol/kg/min for 10 minutes, intravenously) and its precursor BigET (20 and 40 pmol/kg/min for 10 minutes, intravenously) were measured in chronically instrumented swine (n=4) at rest and during submaximal treadmill exercise at 3km/h.Administration of ET resulted in dose‐dependent decreases in CBF and cvPO2 both at rest (P<0.05 by ANOVA) and during exercise (P<0.05 by ANOVA). The decrease in CBF and cvPO2 in response to ET was similar during exercise as compared to rest, indicating that the coronary vasoconstrictor response to ET was maintained during exercise.Administration of BigET also resulted in dose‐dependent decrease in both CBF and cvPO2 at rest (P<0.05 by ANOVA), but not during exercise (P<0.05 by ANOVA). Since exercise resulted in an attenuation of the coronary vasoconstrictor response to BigET but not ET, it appears that the production of ET from its precursor BigET is decreased during exercise.In conclusion, exercise does not result in altered sensitivity of the coronary vasculature to ET, but does affect production of ET from BigET. The decreased ET production is likely to contribute to metabolic coronary vasodilation during exercise.Supported by Netherlands Heart Foundation grant 2000T042.