Angiotensin-converting enzyme inhibition and the norepinephrine spillover response to dynamic exercise

To determine whether prejunctional angiotensin II receptors facilitate norepinephrine (NE) release during exercise, normal volunteers exercised at ~25 or ~65% of maximal O₂ consumption (V̇O(2max)) on two occasions. Steady-state NE kinetics were determined at rest and during exercise by using infusions of [³H]NE. Arterial plasma NE and [³H]NE were determined for calculation of NE spillover and clearance. Before the second bout of exercise at ~25% of V̇O(2max) later that day, enalaprilat (n = 8) or nitroprusside (n = 5) was administered intravenously to lower blood pressure to a comparable level and saline was infused as a time control (n = 4). Exercise at 25% of V̇O(2max) increased heart rate from 73 to 110 beats/min, plasma NE from 296 to 626 pg/ml, and NE spillover from 1.56 to 3.32 nmol · min^-1 · m^-2. The exercise effect was significant in each subgroup. At rest and during exercise, the decrease in blood pressure and the increase in plasma NE and NE spillover were similar with enalaprilat and nitroprusside. There was no drug effect in the saline group. In a separate group (n = 7), exercise at ~65% of V̇O(2max) increased heart rate from 76 to 170 beats/min, plasma NE from 338 to 2,656 pg/ml, and NE spillover from 1.87 to 11.65 nmol · min^-1 · m^-2. In this group, 3 days of oral enalapril did not affect the NE spillover response to exercise. Because the angiotensin-converting enzyme inhibitor did net attenuate the NE spillover response to exercise, we conclude that at the exercise levels tested, prejunctional angiotensin II receptors do not appear to facilitate NE release.