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

Abstract

To determine whether prejunctional angiotensin II receptors facilitate norepinephrine (NE) release during exercise, normal volunteers exercised at approximately 25 or approximately 65% of maximal O2 consumption (VO2max) 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 approximately 25% of VO2max 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 VO2max increased heart rate from 73 to 100 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 approximately 65% of VO2max 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 not 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.

Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle

“…In one human forearm study, intrabrachial AngII infusion during concomitant nitroprusside infusion to offset vasoconstriction was accompanied by an increased concentration of noradrenaline in the forearm venous blood and an increased forearm noradrenaline spillover (Clemson et al 1994). However, several other similar studies, including one by the same group, found no evidence for a functionally significant effect of AngII on noradrenaline release in healthy subjects or in patients with heart failure (Chang et al 1995; Leuenberger et al 1996; Goldsmith et al 1998). In addition, more recent studies, using AT 1 blockade and investigating several vascular beds in humans, have found no support for this mechanism either (Schlaich et al 2005; Krum et al 2006).…”

Acute effects of angiotensin-converting enzyme inhibition versus angiotensin II receptor blockade on cardiac sympathetic activity in patients with heart failure

“…To date, studies examining the functional importance of the sympathoexcitatory effects of angiotensin II have yielded inconsistent results (9, 11, 24, 26 -28, 40 -42, 44, 60, 61). A number of studies, performed in normal volunteers, have failed to define a sympathomodulatory role of the RAS (9,26,41,44,48). Studies examining sympathetic activity in patients with heart failure have yielded conflicting results concerning the importance of angiotensin II as a mediator of sympathetic activity Values are means Ϯ SE.…”