Potentiation of the NO-cGMP pathway and blood flow responses during dynamic exercise in healthy humans.

PURPOSE: Previous work has shown nitric oxide (NO) contributes to ~15% of the hyperemic response to dynamic exercise in healthy humans. This NO-mediated vasodilation occurs, in part, via increases in intracellular cyclic guanosine monophosphate (cGMP), which is catabolized by phosphodiesterase. We sought to examine the effect of phosphodiesterase-5 (PDE-5) inhibition on forearm blood flow (FBF) responses to dynamic handgrip exercise in healthy humans and the role of NO. We hypothesized exercise hyperemia would be augmented by sildenafil citrate (SDF, PDE-5 inhibitor). We further hypothesized any effect of SDF on exercise hyperemia would be abolished with intra-arterial infusion of the NO synthase (NOS) inhibitor L-NG-monomethyl arginine (L-NMMA). METHODS: FBF (Doppler ultrasound) was assessed at rest and during 5 min of dynamic forearm handgrip exercise at 15% of maximal voluntary contraction under control (saline) conditions and during 3 experimental protocols: (1) oral SDF (n = 10), (2) intra-arterial L-NMMA (n = 20), (3) SDF and L-NMMA (n = 10). FBF responses to intra-arterial sodium nitroprusside (NTP, NO donor) were also assessed. RESULTS: FBF increased with exercise (p < 0.01). Intra-arterial infusion of L-NMMA resulted in a reduction in exercise hyperemia (17 ± 1 to 15 ± 1 mL/dL/min, p < 0.01). Although the hyperemic response to NTP was augmented by SDF (area under the curve: 41 ± 7 vs 61 ± 11 AU, p < 0.01), there was no effect of SDF on exercise hyperemia (p = 0.33). CONCLUSIONS: Despite improving NTP-mediated vasodilation, oral SDF failed to augment exercise hyperemia in young, healthy adults. These observations reflect a minor contribution of NO and the cGMP pathway during exercise hyperemia in healthy young humans.

Competition Between Desired Competitive Result, Tolerable Homeostatic Disturbance, and Psychophysiological Interpretation Determines Pacing Strategy.

Scientific interest in pacing goes back >100 years. Contemporary interest, both as a feature of athletic competition and as a window into understanding fatigue, goes back >30 years. Pacing represents the pattern of energy use designed to produce a competitive result while managing fatigue of different origins. Pacing has been studied both against the clock and during head-to-head competition. Several models have been used to explain pacing, including the teleoanticipation model, the central governor model, the anticipatory-feedback-rating of perceived exertion model, the concept of a learned template, the affordance concept, the integrative governor theory, and as an explanation for "falling behind." Early studies, mostly using time-trial exercise, focused on the need to manage homeostatic disturbance. More recent studies, based on head-to-head competition, have focused on an improved understanding of how psychophysiology, beyond the gestalt concept of rating of perceived exertion, can be understood as a mediator of pacing and as an explanation for falling behind. More recent approaches to pacing have focused on the elements of decision making during sport and have expanded the role of psychophysiological responses including sensory-discriminatory, affective-motivational, and cognitive-evaluative dimensions. These approaches have expanded the understanding of variations in pacing, particularly during head-to-head competition.

Cerebrovascular Reactivity and Vascular Activation in Postmenopausal Women With Histories of Preeclampsia.

Cerebrovascular reactivity (CVR) is reduced in patients with cognitive decline. Women with a history of preeclampsia are at increased risk for cognitive decline. This study examined an association between pregnancy history and CVR using a subgroup of 40 age- and parity-matched pairs of women having histories of preeclampsia (n=27) or normotensive pregnancy (n=29) and the association of activated blood elements with CVR. Middle cerebral artery velocity was measured by Doppler ultrasound before and during hypercapnia to assess CVR. Thirty-eight parameters of blood cellular elements, microvesicles, and cell-cell interactions measured in venous blood were assessed for association with CVR using principal component analysis. Middle cerebral artery velocity was lower in the preeclampsia compared with the normotensive group at baseline (63±4 versus 73±3 cm/s; P=0.047) and during hypercapnia (P=0.013-0.056). CVR was significantly lower in the preeclampsia compared with the normotensive group (2.1±1.3 versus 2.9±1.1 cm·s·mm Hg; P=0.009). Globally, the association of the 7 identified principal components with preeclampsia (P=0.107) and with baseline middle cerebral artery velocity (P=0.067) did not reach statistical significance. The interaction between pregnancy history and principal components with respect to CVR (P=0.084) was driven by a nominally significant interaction between preeclampsia and the individual principal component defined by blood elements, platelet aggregation, and interactions of platelets with monocytes and granulocytes (P=0.008). These results suggest that having a history of preeclampsia negatively affects the cerebral circulation years beyond the pregnancy and that this effect was associated with activated blood elements.

Resting sympathetic activity is associated with the sympathetically mediated component of energy expenditure following a meal.

Individuals with high plasma norepinephrine (NE) levels at rest have a smaller reduction in resting energy expenditure (REE) following ß-adrenergic blockade. If this finding extends to the response to a meal, it could have important implications for the role of the sympathetic nervous system in energy balance and weight gain. We hypothesized high muscle sympathetic nerve activity (MSNA) would be associated with a low sympathetically mediated component of energy expenditure following a meal. Fourteen young, healthy adults completed two visits randomized to continuous saline (control) or intravenous propranolol to achieve systemic ß-adrenergic blockade. Muscle sympathetic nerve activity and REE were measured (indirect calorimetry) followed by a liquid mixed meal (Ensure). Measures of energy expenditure continued every 30 min for 5 h after the meal and are reported as an area under the curve (AUC). Sympathetic support of energy expenditure was calculated as the difference between the AUC during saline and ß-blockade (AUCPropranolol-AUCSaline, ß-REE) and as a percent (%) of control (AUCPropranolol÷AUCSaline × 100). ß-REE was associated with baseline sympathetic activity, such that individuals with high resting MSNA (bursts/100 heart beats) and plasma NE had the greatest sympathetically mediated component of energy expenditure following a meal (MSNA: ß-REE R = -0.58, P = 0.03; %REE R = -0.56, P = 0.04; NE: ß-REE R = -0.55, P = 0.0535; %REE R = -0.54, P = 0.0552). Contrary to our hypothesis, high resting sympathetic activity is associated with a greater sympathetically mediated component of energy expenditure following a liquid meal. These findings may have implications for weight maintenance in individuals with varying resting sympathetic activity.

Anaerobic work calculated in cycling time trials of different length.

UNLABELLED: Previous research showed that gross efficiency (GE) declines during exercise and therefore influences the expenditure of anaerobic and aerobic resources. PURPOSE: To calculate the anaerobic work produced during cycling time trials of different length, with and without a GE correction. METHODS: Anaerobic work was calculated in 18 trained competitive cyclists during 4 time trials (500, 1000, 2000, and 4000-m). Two additional time trials (1000 and 4000 m) that were stopped at 50% of the corresponding "full" time trial were performed to study the rate of the decline in GE. RESULTS: Correcting for a declining GE during time-trial exercise resulted in a significant (P<.001) increase in anaerobically attributable work of 30%, with a 95% confidence interval of [25%, 36%]. A significant interaction effect between calculation method (constant GE, declining GE) and distance (500, 1000, 2000, 4000 m) was found (P<.001). Further analysis revealed that the constant-GE calculation method was different from the declining method for all distances and that anaerobic work calculated assuming a constant GE did not result in equal values for anaerobic work calculated over different time-trial distances (P<.001). However, correcting for a declining GE resulted in a constant value for anaerobically attributable work (P=.18). CONCLUSIONS: Anaerobic work calculated during short time trials (<4000 m) with a correction for a declining GE is increased by 30% [25%, 36%] and may represent anaerobic energy contributions during high-intensity exercise better than calculating anaerobic work assuming a constant GE.

The decline in gross efficiency in relation to cycling time-trial length.

PURPOSE: To evaluate whether gross efficiency (GE), determined during submaximal cycling, is lower after time trials and if the magnitude of the decrease differs in relation to race distance. Secondary purposes were to study the rate of the decline in GE and whether changes in muscle-fiber recruitment could explain the decline. METHODS: Cyclists completed 9 GE tests consisting of submaximal exercise performed before and after time trials of different length (500 m, 1000 m, 2000 m, 4000 m, 15,000 m, and 40,000 m). In addition, subjects performed time trials as if they were a 1000-m, 4000-m, or 40,000-m time trial during which they were stopped at 50% of the final time of the preceding "full" time trial. Power output, gas exchange, and EMG were measured continuously throughout the GE tests. RESULTS: A significant interaction effect between distance and time was found for GE (P = .001). GE was significantly lower immediately after the time trials than before (P < .05), and the decline in GE differed between distances (P < .001). GE seemed to decline linearly during the relatively short trials, while it declined more hyperbolically during the 40,000-m. A significant effect of time (P = .04) on mean EMG amplitude was found. However, post hoc comparisons showed no significant differences in mean EMG amplitude between the different time points (before and after the time trials). CONCLUSION: GE decreases during time-trial exercise. Unfortunately, the cause of the decrease remains uncertain. Future modeling studies should consider using a declining instead of a constant GE. In sport situations, the declining GE has to be taken into account when selecting a pacing strategy.