If a competition between the oxygen demands of limb and respiratory muscles happens, hypoxia may favor redistribution of blood flow from peripheral to respiratory muscles during heavy exercise. This hypothesis was tested in eighteen lowlanders and 27 highlanders at 4350m altitude. During an incremental exercise, the regional tissue oxygen saturation (rSO2) and tissue hemoglobin concentration ([Hbt]) of the intercostal muscles and vastus medialis were monitored simultaneously by NIRS. The intercostal and vastus medialis rSO2 values were lower at altitude than at sea level (−10%, p<0.001) and decreased similarly during incremental exercise (p<0.001) while [Hbt] values increased. At maximal exercise, the intercostal rSO2 was lower than the vastus medialis rSO2 in lowlanders (−7%, p<0.001). In highlanders the time patterns were similar but intercostal rSO2 was less decreased at exercise (p<0.05). Maximal exercise performed in hypoxia did not alter the kinetics of rSO2 and [Hbt] in peripheral muscles. These findings do not favor the hypothesis of blood flow redistribution.

Introduction: Both the membrane (Dm) and the capillary (Vc) component of lung diffusing capacity (DL) have been shown to be increased in high altitude residents and to remain essentially unchanged in high altitude sojourners. Maximal exercise has been reported to decrease Dm at sea level (Manier 1993). The effects of high altitude exercise on Dm and Vc as evaluated from the DL for carbon monoxide (DLCO) and nitric oxide (DLNO) respectively, are incompletely understood. Methods: Lowlanders (n=10) and highlanders (n=14) were tested at 4380m above sea level (Cerro de Pasco, Peru); lowlanders also underwent tests at sea level. Spirometry, alveolar volume (VA), DLCO, DLNO, Dm and Vc were assessed (Hypercompact Medisoft, Belgium) using the NO/CO transfer technique. Values were corrected for PcapO 2 , Hb and are presented as mean predicted value (Aguilaniu 2008) ±SEM. Measurements took place at rest and after an endurance test at 80% of VO 2 max at heart rate returned to rest values. Results: Spirometry was normal in all subjects. Hb nor SaO 2 at rest were significantly different between the groups. H pre-E H post-E L pre-E L post-E DLCO/VA % 150±4* 153±4* 125±4 120±3 † DLNO % 143±7* 154±7* † 117±4 110±4 † Vc/VA % 143±5* 145±6* 120±6 113±4 † Dm % 133±5* 140±5* † 110±2 106±3 † H: highlanders, L: Lowlanders; E = endurance. *p<0.05 H vs. L, † p<0.05 pre- vs. post-exercise. At sea level, lowlanders did not demonstrate alterations in diffusion parameters pre- vs. post-endurance test. Conclusion: Strenuous exercise in lowlanders resulted in a decrease of DLCO which was probably caused by interstitial lung edema thickening the alveolocapillary membrane, whereas highlanders were capable of maintaining DLCO-levels by an increase in Dm.

Background: Obstructive sleep apnea (OSA) is strongly correlated with an increased risk of systemic hypertension. However, the link between systemic hypertension and nocturnal apneas remains incompletely understood. Animal studies suggest an implication of the endothelin system. The aim of the study is to determine if endogenous endothelin (ET) plays a role in the increase in blood pressure observed during hypoxic episodes in OSA patients, in addition to peripheral chemoreflex and sympathetic nerve activation. Methods: We assessed the effects of the nonspecific ET antagonist bosentan (500 mg; Tracleer; Actelion; Basel, Switzerland) on ventilation, hemodynamics, and muscle sympathetic nerve activity (MSNA) during normoxia and isocapnic hypoxia using a randomized, crossover, double-blinded, placebo-controlled study design, in 13 severely untreated sleep apneic patients (age 50 ± 9 years, apnea-hypopnea index 44 ± 19 per hour). Results: Hypoxia increased blood pressure, MSNA and minute ventilation as oxygen saturation decreased. Bosentan suppressed completely the increase in systolic blood pressure during a 5 minute hypoxic challenge (143 ± 5 mmHg during hypoxia vs. 133 ± 5 mmHg during normoxia with placebo; 127 ± 3 mmHg during hypoxia vs. 125 ± 3 mmHg during normoxia under bosentan, p = 0.023). Diastolic blood pressure, and the rise in MSNA and ventilation during isocapnic hypoxia did not differ between bosentan and placebo. Conclusion: ET contributes to the rise in systolic pressure in response to acute hypoxia in patients with severely untreated OSA. This was not due to lower chemoreflex activation with bosentan.

Baroreflex activation by a continuous infusion of phenylephrine selectively abolishes the sympathetic nerve activity (MSNA) response to hypoxia in humans. However, whether the reverse is true has, to our knowledge, never been investigated in humans. Studies in animals suggest that this is the case. We tested the hypothesis that deactivation of the baroreceptors enhances the sympathetic response to hypoxia in normal men (mean age of 23 ± 3 years and mean BMI of 22 ± 3 kg.m-2). We compared this response to the one elicited by hypoxia in the presence of baroreflex activation. We recorded in 19 healthy male subjects the hemodynamic, ventilatory and sympathetic variables, during normoxia and hypoxia, in response to continuous intravenous placebo, phenylephrine and nitroprusside infusion. The study was randomized and placebo-controlled. Hypoxia increased MSNA by 159% in the presence of placebo. Both phenylephrine and nitroprusside decreased and increased, respectively, MSNA in the presence of normoxia (36% for phenylephrine and 372% for nitroprusside vs. placebo respectively, both p < 0.004) and hypoxia (49% for phenylephrine and 406% for nitroprusside vs. placebo respectively, both p < 0.007). Thus the sympathetic response to hypoxia is enhanced by baroreflex deactivation and restrained by baroreflex activation. This reveals the new finding that the interaction between the chemo- and baro-receptors is reciprocal in humans.

PURPOSE: Ventilatory stimulation and its chemical control are important when b2 adrenergic agonists are used in asthma treatment. In elite athletes and general population, asthma is a very common condition. Use of beta 2 adrenergic agonists by competitive athletes is strictly prohibited by WADA in sport disciplines due to their assumed ergogenic action, such as an increase of peripheral chemosensitivity and metabolism, in endurance performance and muscle strength. The purpose of the present study is to investigate the effect of salbutamol to chemoreflex and the metaboreflex, its ergogenic contribution in nonasthmatic man. METHODS: Eleven healthy male subjects were measured after 10 μg/min during 30 minutes intravenously salbutamol versus placebo following a double-blind, placebo-controlled, randomized cross-over design. The effects of the beta2-adrenergic agonist, salbutamol, on MSNA, ventilatory responses to hyperoxic hypercapnia (7% CO2 in O2), DVE/DPetCO2, and isocapnic hypoxia (10 % O2 in N2), DVE/DSpO2, and to an isometric muscle contraction followed by a local circulatory arrest (metaboreflex) were determined at rest, followed by an incremental cardiopulmonary exercise test and maximal isokinetic muscle strength test (Cybex). RESULTS: During baseline, HR, SBP, VE and MSNA burst incidence, while MSNA burst frequency, Pet CO2, SaO2 remained unchanged. During hypoxia, HR and VE remained increased, however, MSNA, BP, SaO2, was unchanged during salbutamol compared to placebo. There were no changes in HR, MSNA, VE, SpO2 or PetCO2 during hypercapnia or metaboreflex stimulation with salbutamol. In incremental cardiopulmonary exercise test only Ve/VO2 slope at maximal exercise and O2 pulse at anaerobic threshold were significantly changed by salbutamol, while there were no effects on HR, VO2 max, or other ventilatory equivalents. Salbutamol had any effects on maximal isokinetic muscle strength test (Cybex). CONCLUSIONS: Acute intravenous salbutamol increases Ve at rest stimulating peripheral chemoreceptors with out any changes on aerobic exercise capacity and muscle strength. It is likely that systemic or hemodynamic effects of b2 adrenergic agonist rather than the bronchial actions are involved in the ergogenic effects of salbutamol in healthy subjects.

1. The contribution of peripheral chemoreceptors to the regulation of ventilation during exercise remains incompletely understood. Digoxin has been reported to increase chemoreflex sensitivity in humans. In the present randomized, cross-over, double-blind study, we tested the hypothesis that this increases the ventilatory response to exercise in normal subjects, as assessed by changes in minute ventilation (V(E)) in response to the rate of CO(2) production (VCO(2)). 2. Minute ventilation, end-tidal PCO(2), pulse oximetric O(2) saturation (S(p)O(2)), heart rate and blood pressure (BP) were measured in 11 healthy young male untrained subjects after intravenous infusion of digoxin (0.01 mg/kg) or placebo during normoxia, isocapnic hypoxia and hyperoxic hypercapnoea. All participants underwent a maximum cardiopulmonary exercise test. 3. During normoxia, digoxin increased systolic BP only. During hypoxia, digoxin increased V(E) compared with placebo (P = 0.009) for the same fall in S(p)O(2) (P = NS). Moreover, no significant effects on ventilation and haemodynamic responses were recorded during hypercapnoea. Digoxin increased the V(E) /VCO(2) slope above the anaerobic threshold from 30.4 +/- 2.9 to 32.8 +/- 3.7 (P < 0.05), but did not affect VO(2max). 4. In conclusion, enhanced peripheral chemosensitivity with digoxin increases the ventilatory response to CO(2) production above the anaerobic threshold, but does not affect exercise capacity in healthy humans.

In patients with hypertension, beta blockade decreases muscle sympathetic nerve activity (MSNA; micrographic technique) expressed in burst frequency (burst/min) but does not affect MSNA expressed in burst incidence (burst/100 heart beats), because reductions in blood pressure (BP) upon each diastole continue to deactivate the arterial baroreceptors, but at a slower heart rate (HR). We studied the effects of oral beta blockade on MSNA and baroreflex sensitivity (BRS) in normal participants. Bisoprolol (5 mg, 1 week) was administered in 10 healthy young adults, using a double-blind, placebo-controlled, randomized cross-over study design. The beat-to-beat mean RR interval (RR) and systolic blood pressure (SBP) series were analyzed by power spectral analysis and power computation over the very low frequency (VLF), low frequency, and high frequency (HF) bands. Baroreflex sensitivity was computed from SBP and RR cross-analysis, using time and frequency domain methods. Bisoprolol increased RR (P < .0005), decreased mean SBP and diastolic blood pressure values (P < .01), did not change the SBP and RR powers, except for RR power in VLF (P < .02) and SBP power in HF (P < .03). The MSNA variability (P > .13) and respiratory pattern (P = .84) did not change from placebo to bisoprolol condition. The bisoprolol-induced bradycardia was associated with higher burst/100 heart beats (P < .05) and bisoprolol did not affect burst/min (P = .80). Time domain BRS estimates were increased after bisoprolol (P < .05), while frequency domain ones did not change (P > .1). Oral bisoprolol induces differential effects on sympathetic burst frequency and incidence in normal participants. Peripheral sympathetic outflow over time is preserved as a result of an increased burst incidence, in the presence of a slower HR. Unchanged BP and HR and MSNA variability suggests that the larger burst incidence is not due to sympathetic activation.

Blockade of the skeletal muscle Na+–K+-ATPase pump by digoxin could result in a more marked hyperkaliema during a forearm exercise, which in turn could stimulate the mechano- and metaboreceptors. In a randomized, double-blinded, placebo-controlled, and cross-over-design study, we measured mean blood pressure (MBP), heart rate (HR), ventilation (V E), oxygen saturation (SpO2), muscle sympathetic nerve activity (MSNA), venous plasma potassium and lactic acid during dynamic handgrip exercises, and local circulatory arrest in 11 healthy subjects. Digoxin enhanced MBP during exercise but not during the post-handgrip ischemia and had no effect on HR, V E, SpO2, and MSNA. Venous plasma potassium and lactic acid were also not affected by digoxin-induced skeletal muscle Na+–K+-ATPase blockade. We conclude that digoxin increased MBP during dynamic exercise in healthy humans, independently of changes in potassium and lactic acid. A modest direct sensitization of the muscle mechanoreceptors is unlikely and other mechanisms, independent of muscle reflexes and related to the inotropic effects of digoxin, might be implicated.

The contribution of the peripheral chemoreflex to the ventilatory response to exercise and aerobic exercise capacity remains incompletely understood. Low-dose dopamine has been reported to specifically inhibit the peripheral chemoreceptors. We therefore investigated the effects of intravenous dopamine (3 μg kg−1 min−1) on cardiopulmonary exercise test (CPET) variables in 13 healthy young male subjects. The study was prospective, placebo-controlled, and randomized with more than 24 h between placebo and dopamine administrations. During the CPET, dopamine decreased the V˙E/V˙CO2 output slope (24.61 ± 1.84 vs. 23.09 ± 1.81, placebo vs. Dopamine respectively, p = 0.025), without affecting maximum workload, V˙E and O2 uptake. In conclusion, our study reveals that inhibition of peripheral chemoreflex function with dopamine decreases the V˙E/V˙CO2 slope during dynamic exercise, with no change in aerobic exercise capacity.

BACKGROUND Arterial stiffening is more accelerated in blacks than in whites. Whether this is attributed to an enhanced vascular reactivity to environmental stress stimulation remains unknown. We therefore decided to test the hypothesis that cold pressor test (CPT) elicits a greater increase in arterial stiffness and an enhanced sympathetic skin vasoconstriction in African blacks than in whites normotensives.METHODS A total of 17 young normotensive African blacks and 17 normotensive whites were recruited. All underwent continuous assessment of blood pressure (BP), heart rate,and carotid-femoral pulse wave velocity (PWVc-f) at rest,during and after hand immersion in iced water(CPT). Concomitantly, skin microvascular blood flow was monitored by laser Doppler flowmetry on the opposite hand.RESULTS At baseline, African blacks exhibited higher values of PWVc-f than whites (7.2 +/- 0.3 vs. 6.5 +/- 0.2 m/s, respectively, P = 0.04). During CPT the increases in systolic BP and PWVc-f were greater in African blacks than in whites (systolic BP 17 +/- 2 mm Hg vs. 9 +/- 3 mm Hg, P < 0.001 and PWVc-f 0.62 +/- 0.1 m/s vs. 0.26 +/- 0.1 m/s, P = 0.03, respectively). However, there was no significant difference in the PWVc-f responses among the groups during CPT after adjustment for the increments in mean BR Finally, CPT induced a more pronounced skin microvascular vasoconstriction in African blacks than in whites (-54.4 +/- 5 % vs. -31.3 +/- 6 %, P < 0.001).CONCLUSIONS CPT provokes a more pronounced increase in PWVc-f in normotensive African blacks than in whites, that appears to be due to a greater increase in mean BP. Additionally, African blacks present an intensified skin microvascular response to the CPT as compared to their whites counterparts. Am J Hypertens 2009; 22:958-963 (C) 2009 American Journal of Hypertension, Ltd.