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Background: To determine whether angiotensin II (ANG II) contributes to the reflex skeletal muscle sympathoexcitation elicited by isometric and isotonic exercise, we tested the hypothesis that angiotensin AT(1) receptor blockade (ARB) would attenuate reflex sympathoneural responses to handgrip (HG) and to post-handgrip ischemia (PHGI)., Methods: Seventeen healthy men were studied before and 1 week after random double-blind crossover allocation to oral losartan (100 mg daily) and placebo. Heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded at rest, and during 2 min bouts of isotonic HG at 50% maximum voluntary contraction (MVC) and isometric HG at 30% MVC, performed randomly, each followed by 2 min of PHGI., Results: At rest, losartan doubled plasma renin (P = 0.01) and ANG II (P = 0.03) concentrations, and lowered BP (P < 0.01) yet had no effect on MSNA burst frequency or incidence. HR trended higher (P = 0.060). Losartan's hypotensive effect persisted throughout each exercise bout (P < 0.045). MSNA and HR responses to isotonic exercise and postexercise ischemia were not affected by losartan. Isometric exercise and postexercise ischemia increased MSNA on both sessions (all P < 0.01). Losartan augmented the HR response (P ≤ 0.03), and after losartan MSNA burst frequency (P < 0.01) and incidence (P < 0.04) were significantly higher at all time points, but the magnitude of the MSNA response to isometric exercise and postexercise ischemia was unchanged., Conclusion: In healthy men, short-term ARB does not attenuate reflex sympathoneural responses to HG or PHGI.

Background: Sustained hypotension after an acute dynamic exercise bout is due primarily to peripheral vasodilation. We tested the hypothesis that adenosine-mediated vasodilation contributes to hypotension after exercise, by determining the effect of blocking its actions with caffeine., Methods: Fourteen healthy middle-aged subjects (mean age = 51 +/- 3 years), cycled to peak effort on 2 study days, after a randomized double-blind intravenous infusion of caffeine (4 mg/kg) selective for adenosine receptor blockade, or vehicle. Both studies were performed after 72 h of caffeine abstinence., Results: Infusion achieved 52.0 +/- 6.1 mumol/L caffeine in plasma. Significant reductions in mean and diastolic blood pressure (BP) were elicited by prior exercise on the vehicle day (from 93 +/- 2 to 85 +/- 2 mm Hg v from 79 +/- 2 to 73 +/- 3 mm Hg, respectively; both P < .05), but not after caffeine infusion. Systolic and mean BP, 10 min after exercise, were higher on the caffeine than on the vehicle day (by 9 +/- 3 and 6 +/- 2 mm Hg, respectively; P < .05), as was heart rate (HR) (100 +/- 5 v 93 +/- 4 beats/min; P < .05)., Conclusions: These data suggest that endogenous adenosine contributes to early hypotension after exercise in healthy middle-aged subjects and underscore the importance of caffeine abstinence if BP or HR immediately after exercise is used to infer cardiovascular risk.