Muscle interstitial potassium kinetics during intense exhaustive exercise: effect of previous arm exercise

Interstitial K+ ([K+]i) was measured in human skeletal muscle by microdialysis during exhaustive leg exercise, with (AL) and without (L) previous intense arm exercise. In addition, the reproducibility of the [K+]i determinations was examined. Possible microdialysis-induced rupture of the sarcolemma was assessed by measurement of carnosine in the dialysate, because carnosine is only expected to be found intracellularly. Changes in [K+]i could be reproduced, when exhaustive leg exercise was performed on two different days, with a between-day difference of approximately 0.5 mM at rest and 1.5 mM at exhaustion. The time to exhaustion was shorter in AL than in L (2.7 +/- 0.3 vs. 4.0 +/- 0.3 min; P < 0.05). Furthermore, [K+]i was higher from 0 to 1.5 min of the intense leg exercise period in AL compared with L (9.2 +/- 0.7 vs. 6.4 +/- 0.9 mM; P < 0.001) and at exhaustion (11.9 +/- 0.5 vs. 10.3 +/- 0.6 mM; P < 0.05). The dialysate content of carnosine was elevated by exercise, but low-intensity exercise resulted in higher dialysate carnosine concentrations than subsequent intense exercise. Furthermore, no relationship was found between carnosine concentrations and [K+]i. Thus the present data suggest that microdialysis can be used to determine muscle [K+]i kinetics during intense exercise, when low-intensity exercise is performed before the intense exercise. The high [K+]i levels reached at exhaustion can be expected to cause fatigue, which is supported by the finding that a faster accumulation of interstitial K+, induced by prior arm exercise, was associated with a reduced time to fatigue.     

Precooling leg muscle improves intermittent sprint exercise performance in hot, humid conditions.

We used three techniques of precooling to test the hypothesis that heat strain would be alleviated, muscle temperature (Tmu) would be reduced, and as a result there would be delayed decrements in peak power output (PPO) during exercise in hot, humid conditions. Twelve male team-sport players completed four cycling intermittent sprint protocols (CISP). Each CISP consisted of twenty 2-min periods, each including 10 s of passive rest, 5 s of maximal sprint against a resistance of 7.5% body mass, and 105 s of active recovery. The CISP, preceded by 20 min of no cooling (Control), precooling via an ice vest (Vest), cold water immersion (Water), and ice packs covering the upper legs (Packs), was performed in hot, humid conditions (mean +/- SE; 33.7 +/- 0.3 degrees C, 51.6 +/- 2.2% relative humidity) in a randomized order. The rate of heat strain increase during the CISP was faster in Control than Water and Packs (P < 0.01), but it was similar to Vest. Packs and Water blunted the rise of Tmu until minute 16 and for the duration of the CISP (40 min), respectively (P < 0.01). Reductions in PPO occurred from minute 32 onward in Control, and an increase in PPO by approximately 4% due to Packs was observed (main effect; P < 0.05). The method of precooling determined the extent to which heat strain was reduced during intermittent sprint cycling, with leg precooling offering the greater ergogenic effect on PPO than either upper body or whole body cooling.     

Locomotor muscle fatigue increases cardiorespiratory responses and reduces performance during intense cycling exercise independently from metabolic stress

Locomotor muscle fatigue, defined as an exercise-induced reduction in maximal voluntary force, occurs during prolonged exercise, but its effects on cardiorespiratory responses and exercise performance are unknown. In this investigation, a significant reduction in locomotor muscle force (-18%, P < 0.05) was isolated from the metabolic stress usually associated with fatiguing exercise using a 100-drop-jumps protocol consisting of one jump every 20 s from a 40-cm-high platform. The effect of this treatment on time to exhaustion during high-intensity constant-power cycling was measured in study 1 (n = 10). In study 2 (n = 14), test duration (871 +/- 280 s) was matched between fatigue and control condition (rest). In study 1, locomotor muscle fatigue caused a significant curtailment in time to exhaustion (636 +/- 278 s) compared with control (750 +/- 281 s) (P = 0.003) and increased cardiac output. Breathing frequency was significantly higher in the fatigue condition in both studies despite similar oxygen consumption and blood lactate accumulation. In study 2, high-intensity cycling did not induce further fatigue to eccentrically-fatigued locomotor muscles. In both studies, there was a significant increase in heart rate in the fatigue condition, and perceived exertion was significantly increased in study 2 compared with control. These results suggest that locomotor muscle fatigue has a significant influence on cardiorespiratory responses and exercise performance during high-intensity cycling independently from metabolic stress. These effects seem to be mediated by the increased central motor command and perception of effort required to exercise with weaker locomotor muscles.     

The relationship between plasma potassium concentration and muscle torque during recovery following intense exercise

The present study investigated the relationship between plasma potassium ion concentration ([K⁺]) and skeletal muscle torque during three different 15-min recovery periods after fatigue induced by four 30-s sprints. Four males and one female completed the multiple sprint exercise on three separate days; recovery was passive, i.e. no cycling exercise (PRec), active cycling at 30% peak oxygen consumption O_2peak (30% Rec) and active cycling at 60% O_2peak (60% Rec). Plasma [K⁺] was measured from blood sampled from an antecubital vein of subjects at rest and at 0, 3, 5, 10 and 15 min into each recovery. Isokinetic leg strength was measured at rest and at 1, 6, 11 and 16 min during each recovery. Following the exhaustive sprints, [K⁺] increased significantly from an average mean (SEM) resting value of 3.81 (0.07) mmol · l⁻¹ to 4.48 (0.19) mmol · l⁻¹ (P < 0.01). In all recovery conditions, plasma [K⁺] returned to resting levels within 3 min following the fourth sprint. However, in the two active recovery conditions plasma [K⁺] increased over the remainder of the recovery periods to 4.36 (0.12) mmol · l⁻¹ in the 30% Rec condition and 4.62 (0.12) mmol · l⁻¹ in the 60% Rec condition, the latter being significantly higher than the former (P < 0.01). The maximum torque measured following the sprints decreased significantly, on average, to 61.1 (8.36)% of peak levels (P < 0.01). After 15 min of recovery, maximum torque was highest in the 30% Rec condition at 92.13 (3.06)% of peak levels (P < 0.01), compared to 85.23 (3.64)% and 85.71 (0.82)% for the PRec and 60% Rec conditions, respectively. In contrast to the significant differences in plasma [K⁺] across all three recovery conditions, muscle torque recovery was significantly different in only the 30% Rec condition. In summary, recovery of peak levels of muscle torque following fatiguing exercise does not appear to follow changes in plasma [K⁺]. Accepted: 18 October 1996     

Albumin synthesis after intense intermittent exercise in human subjects

Yang, Roger C., Gary W. Mack, Robert R. Wolfe, and Ethan R. Nadel. Albumin synthesis after intense intermittent exercise inhuman subjects. J. Appl. Physiol.84(2): 584-592, 1998.We measured hepatic albumin synthesis infive volunteers (4 men and 1 woman) at 3 and 6 h after recovery fromintense exercise. A primed-constant infusion of a stable isotopictracer of phenylalanine was used to determine hepatic fractionalsynthetic rate (FSR) and absolute synthetic rate (ASR) of albumin fromthe enrichment of phenylalanine in albumin. The infusion of the stableisotope tracer began 2 h after upright exercise or upright rest.Albumin FSR and ASR were 6.39 ± 0.48%/day and 120 ± 9 mg · kg bodywt¹ · day¹,respectively, 3-6 h after recovery from exercise; the FSR and ASRon the time control study day were 5.94 ± 0.47%/day and 104 ± 9 mg · kg bodywt¹ · day¹,respectively. The 6 and 16% increases(P < 0.05) in FSR and ASR afterexercise were associated with an elevated plasma albumin content at 5 and 6 h of recovery (P < 0.05), anincreased total protein content throughout recovery(P < 0.05), and a negative freewater clearance (P < 0.05) at 2, 3, and 6.5 h of recovery compared with baseline values; these variableswere unchanged from their baselines on the time control study day.Increased albumin content and reduced free water clearance contributeto a retention of fluid within the circulation after intense exercise. The measured increase in albumin synthesis could not account for theentire increase in albumin content at 6 h of recovery from exercise.However, we estimate that if the increased activity was maintained forthe next 18 h, it could account for the expected increase in albumincontent at 24 h of recovery.

     

Caffeine mouth rinse enhances performance,fatigue tolerance and reduces muscle activity during moderate-intensity cycling

We investigated the effects of caffeine mouth rinse on endurance performance, muscle recruitment (i.e., electromyographic activity of the vastus lateralis and rectus femoris), rating of perceived effort and heart rate. Twelve physically-active healthy men cycled at 80% of their respiratory compensation point until task failure. The participants rinsed their mouths for 10 seconds with placebo (PLA, 25 mL of a solution composed of non-caloric mint essence) or caffeine (CAF, 25 mL of 1.2% of anhydrous caffeine concentration with non-caloric mint essence) every 15 minutes of exercise. Time until exhaustion increased 17% (effect size = 0.70) in CAF compared to PLA (p = 0.04). The wavebands of low-frequency electromyographic activity (EMG) of the vastus lateralis and rectus femoris was lower in CAF group than PLA at 50% of the time until exhaustion (p = 0.04). The global EMG signal was lower in CAF group than PLA at 100% of the time until exhaustion (p = 0.001). The rating of perceived effort pooled was higher in CAF mouth rinse (p = 0.001) than PLA group. No effect was found on the heart rate between the groups (p > 0.05). Caffeine mouth rinse increases endurance performance, rating of perceived effort and decreases muscle activity during a moderate-intensity exercise.     

Arterial hypoxemia and performance during intense exercise

In order to determine the level of hypoxemia which is sufficient to impair maximal performance, seven well-trained male cyclists [maximum oxygen consumption (VO_2max)51·min^–1 or 60 ml·kg^–1·min^–1] performed a 5-min performance cycle test to exhaustion at maximal intensity as controlled by the subject, under three experimental conditions: normoxemia [percentage of arterial oxyhemoglobin saturation (%S _a O₂)>94%], and artificially induced mild (%S _aO₂=90±1%) and moderate (%S _aO₂=87±1%) hypoxemia. Performance, evaluated as the total work output (Work_tot) performed in the 5-min cycle test, progressively decreased with decreasing %S _aO₂ [mean (SE) Work_tot=107.40 (4.5) kJ, 104.07 (5.6) kJ, and 102.52 (4.7) kJ, under normoxemia, mild, and moderate hypoxemia, respectively]. However, only performance in the moderate hypoxemia condition was significantly different than in normoxemia (P=0.02). Mean oxygen consumption and heart rate were similar in the three conditions (P=0.18 andP=0.95, respectively). End-tidal partial pressure of CO₂ was significantly lower (P=0.005) during moderate hypoxemia compared with normoxemia, and ventilatory equivalent of CO₂ was significantly higher (P=0.005) in both hypoxemic conditions when compared with normoxemia. It is concluded that maximal performance capacity is significantly impaired in highly trained cyclists working under an %S _aO₂ level of 87% but not under a milder desaturation level of 90%.     

Blood lactate accumulation in intermittent supramaximal exercise

Blood lactate accumulation rate and oxygen consumption have been studied in six trained male runners, aged 20 to 30 years. Subjects ran on a treadmill at a rate representing 172 +/- 5% VO2max for four 45 s sessions, separated by 9 min rest periods. Oxygen consumption was measured throughout. Blood lactate was determined in samples taken from the ear and VO2 was measured at the end of each exercise session, and two, five and nine minutes later. After the fourth exercise session, the same measurements were made every five min for 30 min. 4 subjects repeated a single exercise of the same type, duration and intensity and the same measurements were taken. With repetitive intermittent exercise, gradual increases in blood lactate concentration [( LA]b) occurred, whereas its rate of accumulation (delta[LA]b) decreased. The amount of oxygen consumed during each 45 s exercise session remained unchanged for a given subject. After cessation of intermittent exercise, the half-time of blood lactate was 26 min, whereas it was only 15 min after a single exercise session. VO2 values, on the other hand, returned to normal after 15 to 20 min. All other conditions being equal, the gradual decrease in delta[LA]b during intermittent exercise could be explained if the lactate produced during the first exercise session is used during the second period, and/or if the diffusion space of lactate increases. The diffusion space seems to be multi-compartmental on the basis of half-time values noted for [LA]b after intermittent exercise, compared with those noted after a single exercise session.(ABSTRACT TRUNCATED AT 250 WORDS)     

Wearing a cooling jacket during exercise reduces thermal strain and improves endurance exercise performance in a warm environment

The aim of the present study was to investigate the effect of wearing a cooling jacket on thermoregulatory responses and endurance exercise performance in a warm environment. Nine untrained male subjects cycled for 60 minutes at 60% Vo(2)max (Ex1) and then immediately exercised to exhaustion at 80% Vo(2)max (Ex2) in 32.0 +/- 0.2 degrees C and 70-80% relative humidity. Four separate conditions were set during exercise: no water intake (NW), water intake (W), wearing a cooling jacket (C) and the combination of C and W (C+W). Rectal temperatures (T(re)) before Ex1 were not different between the 4 conditions, whereas at the end of Ex1 T(re) of C+W was significantly lower than the C and W (p < 0.05). Mean skin temperature (T(sk)) was significantly lower in C and C+W than the NW and W during Ex1. Heart rate of C and C+W were significantly lower than the NW and W, and rating of perceived exertion (RPE) in C+W was lower than in the other conditions. Exercise time to exhaustion was significantly longer in C+W than in the other conditions (NW < W, C < C+W; p < 0.05), whereas T(re) at exhaustion was not different. Our results indicate that the combination of wearing a cooling jacket and water intake enhances exercise endurance performance in a warm environment because of a widened temperature margin before the critical limiting temperature is reached and also because of decreased thermoregulatory and cardiovascular strain.     

Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance.

This study investigated creatine supplementation (CrS) effects on muscle total creatine (TCr), creatine phosphate (CrP), and intermittent sprinting performance by using a design incorporating the time course of the initial increase and subsequent washout period of muscle TCr. Two groups of seven volunteers ingested either creatine [Cr; 6 x (5 g Cr-H(2)O + 5 g dextrose)/day)] or a placebo (6 x 5 g dextrose/day) over 5 days. Five 10-s maximal cycle ergometer sprints with rest intervals of 180, 50, 20, and 20 s and a resting vastus lateralis biopsy were conducted before and 0, 2, and 4 wk after placebo or CrS. Resting muscle TCr, CrP, and Cr were unchanged after the placebo but were increased (P < 0.05) at 0 [by 22.9 +/- 4.2, 8.9 +/- 1.9, and 14.0 +/- 3.3 (SE) mmol/kg dry mass, respectively] and 2 but not 4 wk after CrS. An apparent placebo main effect of increased peak power and cumulative work was found after placebo and CrS, but no treatment (CrS) main effect was found on either variable. Thus, despite the rise and washout of muscle TCr and CrP, maximal intermittent sprinting performance was unchanged by CrS.     

Creatine reduces human muscle PCr and pH decrements and P(i) accumulation during low-intensity exercise.

The purpose of this study was to examine with (31)P-magnetic resonance spectroscopy energy metabolism during repeated plantar flexion isometric exercise (Ex-1-Ex-4) at 32 +/- 1 and 79 +/- 4% of maximal voluntary contraction (MVC) before and during a creatine (Cr) feeding period of 5 g/day for 11 days. Eight trained male subjects participated in the study. ATP was unchanged with Cr supplementation at rest and during exercise at both intensities. Resting muscle phosphocreatine (PCr) increased (P < 0.05) from 18.3 +/- 0.9 (before) to 19.6 +/- 1.0 mmol/kg wet wt after 9 days. At 79% MVC, PCr used, P(i) accumulated, and pH at the end of Ex-1-Ex-4 were similar after 4 and 11 days of Cr supplementation. In contrast, PCr utilization and P(i) accumulation were lower and pH was higher for exercise at 32% MVC with Cr supplementation, suggesting aerobic resynthesis of PCr was more rapid during exercise. These results suggest that elevating muscle Cr enhances oxidative phosphorylation during mild isometric exercise, where it is expected that oxygen delivery matches demands and predominantly slow-twitch motor units are recruited.     

Muscle metabolites and performance during high-intensity, intermittent exercise

Six men werestudied during four 30-s "all-out" exercise bouts on anair-braked cycle ergometer. The first three exercise bouts wereseparated by 4 min of passive recovery; after the third bout, subjectsrested for 4 min, exercised for 30 min at 30-35% peakO₂ consumption, and rested for afurther 60 min before completing the fourth exercise bout. Peak powerand total work were reduced (P < 0.05) during bout 3 [765 ± 60 (SE) W; 15.8 ± 1.0 kJ] compared withbout 1 (1,168 ± 55 W, 23.8 ± 1.2 kJ), but no difference in exercise performance was observed betweenbouts 1 and4 (1,094 ± 64 W, 23.2 ± 1.4 kJ). Before bout 3, muscle ATP,creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum (SR)Ca²⁺ uptake were reduced, whilemuscle lactate and inosine 5'-monophosphate wereincreased. Muscle ATP and glycogen before bout4 remained lower than values beforebout 1 (P < 0.05), but there were no differences in muscle inosine 5'-monophosphate, lactate, pH, and SR Ca²⁺ uptake. Muscle CP levelsbefore bout 4 had increased aboveresting levels. Consistent with the decline in muscle ATP wereincreases in hypoxanthine and inosine before bouts3 and 4. The decline in exercise performance does not appear to be related to a reduction inmuscle glycogen. Instead, it may be caused by reduced CP availability, increased H⁺ concentration,impairment in SR function, or some other fatigue-inducing agent.

     

Skeletal muscle RAS and exercise performance

A local renin-angiotensin system (RAS) may be suggested by evidence of gene expression of RAS components within the tissue as well as physiological responsiveness of this gene expression. This review will focus on the evidence supporting the existence of the constituent elements of a physiologically functional paracrine muscle RAS. The effect of local skeletal muscle RAS on human exercise performance will be explored via its relation with pharmacological intervention and genetic studies.The most likely configuration of the muscle RAS is a combination of in situ synthesis and uptake from the circulation of RAS components. A reduction in angiotensin-converting enzyme (ACE) activity reverses the decline in physical performance due to peripheral muscle factors in those with congestive heart failure and may halt or slow decline in muscle strength in elderly women. Genetic studies suggest that increased ACE and angiotensin II (Ang II) mediate greater strength gains perhaps via muscle hypertrophy whereas lower ACE levels and reduced bradykinin (BK) degradation mediate enhanced endurance performance perhaps via changes in substrate availability, muscle fibre type and efficiency.     

Caffeine, performance, and metabolism during repeated Wingate exercise tests

Investigations examining the ergogenicand metabolic influence of caffeine during short-term high-intensityexercise are few in number and have produced inconsistent results. Thisstudy examined the effects of caffeine on repeated bouts ofhigh-intensity exercise in recreationally active men. Subjects(n = 9) completed four 30-s Wingate(WG) sprints with 4 min of rest between each exercise bout on twoseparate occasions. One hour before exercise, either placebo (Pl;dextrose) or caffeine (Caf; 6 mg/kg) capsules were ingested. Caf ingestion did not have any effect on poweroutput (peak or average) in the first two WG tests and had a negative effect in the latter two exercise bouts. Plasmaepinephrine concentration was significantly increased 60 min after Cafingestion compared with Pl; however, this treatment effect disappearedonce exercise began. Caf ingestion had no significant effect on bloodlactate, O₂ consumption, oraerobic contribution at any time during the protocol. After the secondWingate test, plasma NH₃concentration increased significantly from the previous WG test and wassignificantly higher in the Caf trial compared with Pl. These datademonstrate no ergogenic effect of caffeine on power output duringrepeated bouts of short-term, intense exercise. Furthermore, there was no indication of increased anaerobic metabolism after Caf ingestion with the exception of an increase inNH₃ concentration.

     

Factors influencing hydrogen ion concentration in muscle after intense exercise

To assess the importance of factors influencing the resolution of exercise-associated acidosis, measurements of acid-base variables were made in nine healthy subjects after 30 s of maximal exercise on an isokinetic cycle ergometer. Quadriceps muscle biopsies (n = 6) were taken at rest, immediately after exercise, and at 3.5 and 9.5 min of recovery; arterial and femoral venous blood were sampled (n = 3) over the same time. Intracellular and plasma inorganic strong ions were measured by neutron activation and ion-selective electrodes, respectively; lactate concentration ([La-]) was measured enzymatically, and plasma PCO2 and pH were measured by electrodes. Immediately after exercise, intracellular [La-] increased to 47 meq/l, almost fully accounting for a reduction in intracellular strong ion difference ([SID]) from 154 to 106 meq/l. At the same time, femoral venous PCO2 increased to 100 Torr and plasma [La-] to 9.7 meq/l; however, plasma [SID] did not change because of a concomitant increase in inorganic [SID] secondary to increases in [K+], [Na+], and [Ca2+]. During recovery, muscle [La-] fell to 26 meq/l by 9.5 min; [SID] remained low (101 and 114 meq/l at 3.5 and 9.5 min, respectively) due almost equally to the elevated [La-] (30 and 26 meq/l) and reductions in [K+] (from 142 meq/l at rest to 123 and 128 meq/l). Femoral venous PCO2 rose to 106 Torr at 0.5 min postexercise and fell to resting values at 9.5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic response of equine muscle to intermittent maximal exercise

Four thoroughbred horses performed 4 gallops (G1-G4) with intervals of 5 min. With one exception, gallops were sustained at maximal speed over 620 m. Muscle biopsy samples of the middle gluteal and brachiocephalicus were taken before, during, and after exercise and assayed for ATP and intermediary metabolites. The results showed a major involvement of the brachiocephalicus, in addition to the middle gluteal, during galloping. In three horses, who were clearly fatigued, muscle ATP decreased by up to 50% by the end of G4. This was matched by an equal rise in inosine 5'-monophosphate. Pronounced accumulations of glycerol 3-phosphate, glycerol, and lactate (up to 204 mmol X kg dry muscle-1) occurred with exercise. In the fourth horse, which was less fatigued, a decrease in ATP and increases in intermediary metabolites were much less. Postexercise there was little or no recovery in muscle ATP or lactate during 30 min. The decreases in ATP are consistent with a high activity of adenosine 5'-monophosphate deaminase in horse muscle and indicative also of the high level of anaerobic stress of the exercise program. There was evidence to suggest that the increase in muscle glycerol resulted from hydrolysis of glycerol 3-phosphate and not from the utilization of triglyceride.     

Effects of alkalosis on muscle ions at rest and with intense exercise

The effects of metabolic and respiratory alkalosis (MALK and RALK) on intracellular strong ion concentrations ([ion]i) and muscle to blood ion fluxes were examined at rest and during 5 min of intense, intermittent tetanic stimulation in the isolated, perfused rat hindlimb. Compared with the control (C), perfusion of resting skeletal muscle during MALK and RALK significantly increased [Cl-]i and [Na+]i, and RALK significantly lowered [K+]i; these changes, however, did not affect initial hindlimb force production. In both resting and stimulated muscle, the intracellular ion changes corresponded to appropriate perfusate to muscle ion fluxes. At rest, changes in slow-twitch soleus were greater than in fast-twitch white gastrocnemius (WG), but stimulation-induced changes in [Lac]i and [K+]i were greater in WG. At the end of stimulation [K+]i and [Mg2+]i had decreased less in MALK than in C and RALK, particularly in plantaris and WG muscles. Compared with C, the muscle to perfusate flux of Lac- increased by 37% in MALK and 27% in RALK. This was associated with significantly less Lac- accumulation in all muscles in MALK than in RALK, which, in turn, had significantly less lactate than C. Lactate efflux from contracting skeletal muscle was significantly correlated with an uptake of Cl- by muscle. It is concluded that extracellular alkalosis alters skeletal muscle intracellular ionic composition and increases Lac- efflux from skeletal muscle. In agreement with other studies, lactate release appears to occur by both ionic and molecular transport processes. Alkalosis had no apparent effect on muscle performance with this preparation.     

Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia

Chronic intermittent hypoxia (IH) during sleep can result from obstructive sleep apnea (OSA), a disorder that is particularly prevalent in obesity. OSA is associated with high levels of circulating leptin, cardiovascular dysfunction, and dyslipidemia. Relationships between leptin and cardiovascular function in OSA and chronic IH are poorly understood. We exposed lean wild-type (WT) and obese leptin-deficient ob/ob mice to IH for 4 wk, with and without leptin infusion, and measured cardiovascular indices including aortic vascular stiffness, endothelial function, cardiac myocyte morphology, and contractile properties. At baseline, ob/ob mice had decreased vascular compliance and endothelial function vs. WT mice. We found that 4 wk of IH decreased vascular compliance and endothelial relaxation responses to acetylcholine in both WT and leptin-deficient ob/ob animals. Recombinant leptin infusion in both strains restored IH-induced vascular abnormalities toward normoxic WT levels. Cardiac myocyte morphology and function were unaltered by IH. Serum cholesterol and triglyceride levels were significantly decreased by leptin treatment in IH mice, as was hepatic stearoyl-Coenzyme A desaturase 1 expression. Taken together, these data suggest that restoring normal leptin signaling can reduce vascular stiffness, increase endothelial relaxation, and correct dyslipidemia associated with IH.