Muscle blood flow and vasodilation are blunted at the onset of exercise following an acute bout of ischemia-reperfusion.

Ischemia-reperfusion (I/R) injury can attenuate endothelial function and impair nitric oxide bioavailability. We tested the hypothesis that I/R also blunts the rapid and steady-state hyperemic and vasodilatory responses to handgrip exercise. Ten subjects (8M/2F; 24 ± 4 yr) performed handgrip exercises before and after I/R (20 min of ischemia/20 min of reperfusion) and time control (40-min supine rest) trials. Forearm blood flow (FBF) and forearm vascular conductance (FVC) were assessed with Doppler ultrasound during single forearm contractions and 3 min of rhythmic handgrip exercise. Venous blood samples were drawn at rest and during exercise to assess plasma [nitrite]. Peak ΔFBF (from baseline) and ΔFVC following single contractions were attenuated following I/R (134 ± 48 vs. 103 ± 42 mL·min-1; 160 ± 55 vs. 118 ± 48 mL·min-1·100 mmHg-1, P < 0.05 for both), but not following time control (115 ± 63 vs. 124 ± 57 mL·min-1; 150 ± 80 vs. 148 ± 64 mL·min-1·100 mmHg-1, P = 0.16 and P = 0.95, respectively). Steady-state ΔFBF and ΔFVC during rhythmic exercise were unchanged in both I/R (192 ± 52 vs. 190 ± 53 mL·min-1; 208 ± 56 vs. 193 ± 60 mL·min-1·100 mmHg-1) and time control (188 ± 54 vs. 196 ± 48 mL·min-1; 206 ± 60 vs. 207 ± 49 mL·min-1·100 mmHg-1) trials (group × time interactions P = 0.34 and 0.21, respectively). Plasma [nitrite] under resting conditions and during steady-state rhythmic exercise was attenuated following I/R (P < 0.05 for both), but not following time control (P = 0.54 and 0.93). These data indicate that I/R blunts hyperemia and vasodilation at the onset of muscle contractions but does not attenuate these responses during steady-state exercise.NEW & NOTEWORTHY Ischemia-reperfusion can impair endothelial function; however, it remains unknown whether exercise hyperemia and vasodilation are also impaired. This study presents novel findings that ischemia-reperfusion blunts the hyperemic and vasodilatory responses at the onset of muscle contractions but not during steady-state exercise. Plasma [nitrite] was also blunted at baseline and during steady-state exercise following ischemia-reperfusion compared with time control. These attenuated responses at the onset of exercise may be associated with ischemia-reperfusion reductions in NO bioavailability.

Acute inorganic nitrate supplementation and the hypoxic ventilatory response in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) have increased cardiovascular disease risk largely attributable to hypertension. Heightened peripheral chemoreflex sensitivity (i.e., exaggerated responsiveness to hypoxia) facilitates hypertension in these patients. Nitric oxide blunts the peripheral chemoreflex, and patients with OSA have reduced nitric oxide bioavailability. We therefore investigated the dose-dependent effects of acute inorganic nitrate supplementation (beetroot juice), an exogenous nitric oxide source, on blood pressure and cardiopulmonary responses to hypoxia in patients with OSA using a randomized, double-blind, placebo-controlled crossover design. Fourteen patients with OSA (53 ± 10 yr, 29.2 ± 5.8 kg/m2, apnea-hypopnea index = 17.8 ± 8.1, 43%F) completed three visits. Resting brachial blood pressure and cardiopulmonary responses to inspiratory hypoxia were measured before, and 2 h after, acute inorganic nitrate supplementation [∼0.10 mmol (placebo), 4.03 mmol (low dose), and 8.06 mmol (high dose)]. Placebo increased neither plasma [nitrate] (30 ± 52 to 52 ± 23 µM, P = 0.26) nor [nitrite] (266 ± 153 to 277 ± 164 nM, P = 0.21); however, both increased following low (29 ± 17 to 175 ± 42 µM, 220 ± 137 to 514 ± 352 nM) and high doses (26 ± 11 to 292 ± 90 µM, 248 ± 155 to 738 ± 427 nM, respectively, P < 0.01 for all). Following placebo, systolic blood pressure increased (120 ± 9 to 128 ± 10 mmHg, P < 0.05), whereas no changes were observed following low (121 ± 11 to 123 ± 8 mmHg, P = 0.19) or high doses (124 ± 13 to 124 ± 9 mmHg, P = 0.96). The peak ventilatory response to hypoxia increased following placebo (3.1 ± 1.2 to 4.4 ± 2.6 L/min, P < 0.01) but not low (4.4 ± 2.4 to 5.4 ± 3.4 L/min, P = 0.11) or high doses (4.3 ± 2.3 to 4.8 ± 2.7 L/min, P = 0.42). Inorganic nitrate did not change the heart rate responses to hypoxia (beverage-by-time P = 0.64). Acute inorganic nitrate supplementation appears to blunt an early-morning rise in systolic blood pressure potentially through suppression of peripheral chemoreflex sensitivity in patients with OSA.NEW & NOTEWORTHY The present study is the first to examine the acute effects of inorganic nitrate supplementation on resting blood pressure and cardiopulmonary responses to hypoxia (e.g., peripheral chemoreflex sensitivity) in patients with obstructive sleep apnea (OSA). Our data indicate inorganic nitrate supplementation attenuates an early-morning rise in systolic blood pressure potentially attributable to blunted peripheral chemoreflex sensitivity. These data show proof-of-concept that inorganic nitrate supplementation could reduce the risk of cardiovascular disease in patients with OSA.