Effects of 12 weeks of aerobic exercise on body composition and vascular compliance in obese boys.

AIM: This study tested the hypothesis that 12 weeks of air board exercise would enhance cardiorespiratory fitness and vascular compliance and reduce % body fat in obese Korean boys. METHODS: Twenty-two obese boys (>30% body fat) were studied. They were divided into 2 groups- an aerobic exercise group (N.=12), which trained 3 days/week, 50 min/day for 12 weeks, and a control group (N.=10). Control subjects only performed activities involved in their physical education classes. Body composition, cardiovascular fitness (20 m multistage endurance test performance) and vascular compliance were assessed before and after the completion of exercise training. RESULTS: The % changes in body fat (-4.6±0.9 vs. -1.5±1.0%), fat mass (-5.4±1.5 vs. -0.1±1.6%) and performance on the cardiovascular fitness test (14.3±2.5 vs. 3.7±1.6%) were greater in the exercise group than in the controls Compared to controls, % increases in vascular compliance were greater in the arms and legs of the exercise group (left arm: 2.8±0.5 vs. 2.0±2.9%; left leg: 2.6±1.2 vs. -0.5±2.0%; right arm: 2.9±0.9 vs. 0.3±2.9%; right leg: 4.8±1.8 vs. 1.5±2.0%). CONCLUSION: Results suggest that exercise training can reduce % body fat and enhance vascular compliance in obese male adolescents; changes that may reduce the risk for later development of cardiovascular disease.

Cardiovascular effects of cadence and workload.

Increases in cadence may augment SV during submaximal cycling (> 65 % VO2max) via effects of increased muscle pump activity on preload. At lower workloads (45 - 65 % VO2max), SV tends to plateau, suggesting that effects of increases in cadence on pump activity have little influence on SV. We hypothesized that cadence-induced increases in CO at submaximal workloads, where SV tends to plateau, are due to elevations in HR and/or O2 extraction. SV, CO, HR, VO2, and delta a - vO2 were assessed at 80 and 100 rpm during workloads of 50 % (LO) or 65 % (HI) of VO2max in 11 male cyclists. No changes in SV were seen. CO was higher at 100 rpm in 10 of 11 subjects at LO (18.1 +/- 2.7 vs. 17.2 +/- 2.6 L/min). VO2 at both workloads was greater at 100 than 80 rpm as was HR (LO: 129 +/- 11 vs. 121 +/- 10 beats/min; HI: 146 +/- 13 vs. 139 +/- 14 beats/min) (p < 0.05). delta a - vO2 was greater at HI compared to LO at 80 (15.1 +/- 1.6 vs. 13.6 +/- 1.3 ml) and 100 rpm (16.0 +/- 1.7 vs. 15.1 +/- 1.6 ml) (p < 0.05). Results suggest that increases in O2 demand during low submaximal cycling (50 % VO2max) at high cadences are met by HR-induced increases in CO. At higher workloads (65 % VO2max), inability of higher cadences to increase CO and O2 delivery is offset by greater O2 extraction.

Effects of nitric oxide synthase inhibition on vascular conductance during high speed treadmill exercise in rats.

To determine the functional role of nitric oxide (NO) in regulating vascular conductance during high intensity dynamic exercise in skeletal muscles composed of all major fibre types, female Wistar rats (277 +/- 4 g; n = 7) were run on a motor-driven treadmill at a speed and gradient (60 m min(-1), 10 % gradient) established to yield maximal oxygen uptake (V(O2,max)). Vascular conductance (ml min(-1) (100 g)(-1) mmHg(-1)), defined as blood flow normalised to mean arterial pressure (MAP), was determined using radiolabelled microspheres during exercise before and after NO synthase (NOS) inhibition with N (G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1), I.A.). The administration of L-NAME increased MAP from pre-L-NAME baseline values, demonstrating that NOS activity is reduced. The administration of L-NAME also reduced vascular conductance in 20 of the 28 individual hindlimb muscles or muscle parts examined during high speed treadmill exercise. These reductions in vascular conductance correlated linearly with the estimated sum of the percentage of slow twitch oxidative (SO) and fast twitch oxidative glycolytic (FOG) types of fibres in each muscle (Deltaconductance = -0.0082(%SO + %FOG) - 0.0105; r = 0.66; P < 0.001). However, if the reduction in vascular conductance found in the individual hindquarter muscles or muscle parts was expressed as a percentage decrease from the pre-L-NAME value (%Delta = (pre-L-NAME conductance - post-L-NAME conductance)/ pre-L-NAME conductance x 100), then the reduction in vascular conductance was similar in all muscles examined (average %Delta = -23 +/- 2 %). These results suggest that NO contributes substantially to the regulation of vascular conductance within and among muscles of the rat hindquarter during high intensity exercise. When expressed in absolute terms, the results suggest that the contribution of NO to the regulation of vascular conductance during high intensity exercise is greater in muscles that possess a high oxidative capacity. In contrast, if results are expressed in relative terms, then the contribution of NO to the regulation of vascular conductance during high intensity exercise is similar across the different locomotor muscles located in the rat hindlimb and independent of the fibre type composition.

Central and peripheral effects of angiotensin II on the cardiovascular response to exercise.

The authors tested the hypothesis that angiotensin II modulates cardiovascular responses to dynamic exercise via peripheral and central effects on the autonomic nervous system. Ten subjects performed three identical exercise tests during treatment with placebo, valsartan (an angiotensin II type 1 receptor blocker), or enalapril (an angiotensin-converting enzyme inhibitor). With placebo, plasma concentrations of angiotensin II, norepinephrine, and epinephrine were elevated during cycling at 80% of heart rate reserve (HRR). Enalapril attenuated increases in heart rate, mean arterial pressure (MAP), and catecholamines during cycling, whereas valsartan only attenuated MAP and rate-pressure product above 60% HRR, and norepinephrine. The different responses provoked by the two drug treatments suggest that angiotensin-converting enzyme inhibition affects cardiovascular responses to exercise by mechanisms unrelated to production of angiotensin II. Indices of autonomic function during dynamic exercise were not changed by either drug. Attenuation of norepinephrine release during exercise by valsartan suggests that angiotensin II facilitates the release of norepinephrine from sympathetic postganglionic neurons. Angiotensin II, therefore, contributes to the pressor response to exercise by inducing peripheral vasoconstriction and facilitation of norepinephrine release from postganglionic sympathetic nerve endings that are unrelated to central activation of the autonomic nervous system.

Effects of caffeine and high ambient temperature on haemodynamic and body temperature responses to dynamic exercise.

Caffeine can enhance mean arterial blood pressure (MAP) and attenuate forearm blood flow (FBF) and forearm vascular conductance (FVC) during exercise in thermal neutral conditions without altering body temperature. During exercise at higher ambient temperatures, where a greater transfer of heat from the body core to skin would be expected, caffeine-induced attenuation of FBF (i.e. cutaneous blood flow) could attenuate heat dissipation and increase body temperature (T(re)). We hypothesized that during exercise at an ambient temperature of 38 degrees C, caffeine increases MAP, and attenuates FBF and FVC such that T(re) is increased. Eleven caffeine-naive, active men, were studied at rest and during exercise after ingestion of a placebo or 6 mg kg(-1) of caffeine. MAP, heart rate (HR), FBF, FVC, T(re) skin temperature (T(sk)) and venous lactate concentrations (lactate) were assessed sequentially during rest at room temperature, after 45 min of exposure to an ambient temperature of 38 degrees C, and during 35 min of submaximal cycling. Heat exposure caused increases in MAP, FBF, FVC and T(sk) that were not altered by caffeine. HR, T(re), and lactate were unaffected. During exercise, only MAP (95 +/- 2 vs. 102 +/- 2 mmHg), HR (155 +/- 10 vs. 165 +/- 10 beats min(-1)), and lactate (2.0 +/- 0.4 vs. 2.3 +/- 0.4 mmol l(-1)) were increased by caffeine. These data indicate that increases in cutaneous blood flow during exercise in the heat are not reduced by caffeine. This may be because of activation of thermal reflexes that cause cutaneous vasodilation capable of offsetting caffeine-induced reductions in blood flow. Caffeine-induced increases in lactate, MAP and HR during exercise suggest that this drug and high ambient temperatures increase production of muscle metabolites that cause reflex cardiovascular responses.

Hemodynamic responses to static and dynamic muscle contractions at equivalent workloads.

We tested the hypothesis that static contraction causes greater reflex cardiovascular responses than dynamic contraction at equivalent workloads [i.e., same tension-time index (TTI), holding either contraction time or peak tension constant] in chloralose-anesthetized cats. When time was held constant and tension was allowed to vary, dynamic contraction of the hindlimb muscles evoked greater increases (means +/- SE) in mean arterial pressure (MAP; 50 +/- 7 vs. 30 +/- 5 mmHg), popliteal blood velocity (15 +/- 3 vs. 5 +/- 1 cm/s), popliteal venous PCO(2) (15 +/- 3 vs. 3 +/- 1 mmHg), and a greater decrease in popliteal venous pH (0.07 +/- 0.01 vs. 0.03 +/- 0.01), suggesting greater metabolic stimulation during dynamic contraction. Similarly, when peak tension was held constant and time was allowed to vary, dynamic contraction evoked a greater increase in blood velocity (13 +/- 1 vs. -1 +/- 1 cm/s) without causing any differences in other variables. To investigate the reflex contribution of mechanoreceptors, we stretched the hindlimb dynamically and statically at the same TTI. A larger reflex increase in MAP during dynamic stretch (32 +/- 8 vs. 24 +/- 6 mmHg) was observed when time was held constant, indicating greater mechanoreceptor stimulation. However, when peak tension was held constant, there were no differences in the reflex cardiovascular response to static and dynamic stretch. In conclusion, at comparable TTI, when peak tension is variable, dynamic muscle contraction causes larger cardiovascular responses than static contraction because of greater chemical and mechanical stimulation. However, when peak tensions are equivalent, static and dynamic contraction or stretch produce similar cardiovascular responses.

Static contraction causes a reflex-induced release of arginine vasopressin in anesthetized cats.

We tested the hypothesis that brief static contraction of the triceps surae muscle causes reflex-induced increases in plasma arginine vasopressin (AVP) in anesthetized cats. Arterial blood samples, for measurement of plasma AVP, were taken before and after 30 s of electrically stimulated static contraction performed at a low intensity (<20% of maximal; n = 5), a high intensity (>70% of maximal; n = 7), and a high intensity after denervation of the triceps surae (n = 5). The low intensity contraction protocol was repeated during alpha-adrenergic blockade (n = 7) to minimize potential baroreflex-induced inhibition of AVP release. Passive stretch of the triceps surae was conducted (n = 5) to determine effects of muscle mechanoreceptor stimulation on the release of AVP. Low intensity contraction had no effect on plasma AVP. During alpha-adrenergic blockade, this same contraction intensity caused this peptide to increase from 12.8 +/- 2.1 to 17.7 +/- 2.6 pg/ml. High intensity contraction caused an increase in AVP (13.2 +/- 3.5 to 26.1 +/- 6.6 pg/ml) that was abolished by denervation (14.4 +/- 3. 7 vs. 17.1 +/- 6.6 pg/ml). Passive stretch had no effect on plasma AVP. These findings suggest that brief static contraction causes increases in plasma AVP that are reflex in nature, intensity dependent, opposed by the arterial baroreflex, and probably unrelated to muscle mechanoreceptor activation.

Microvascular and myocardial contractile responses to ischemia: influence of exercise training.

We hypothesized that exercise training preserves endothelium-dependent relaxation, lessens receptor-mediated constriction of coronary resistance arteries, and reduces myocardial contractile dysfunction in response to ischemia. After 10 wk of treadmill running or cage confinement, regional and global indexes of left ventricular contractile function were not different between trained and sedentary animals in response to three 15-min periods of ischemia (long-term; n = 17), one 5-min bout of ischemia (short-term; n = 18), or no ischemia (sham-operated; n = 24). Subsequently, coronary resistance vessels ( approximately 106 +/- 4 microm ID) were isolated and studied using wire myographs. Maximal ACh-evoked relaxation was approximately 25, 40, and 60% of KCl-induced preconstriction after the long-term, short-term, and sham-operated protocols, respectively, and was similar between groups. Maximal sodium nitroprusside-evoked relaxation also was similar between groups among all protocols, and vasoconstrictor responses to endothelin-1 and U-46619 were not different in trained and sedentary rats after short-term ischemia or sham operation. We did observe that, after long-term ischemia, maximal tension development in response to endothelin-1 and U-46619 was blunted (P < 0.05) in trained animals by approximately 70 and approximately 160%, respectively. These results support our hypothesis that exercise training lessens receptor-mediated vasoconstriction of coronary resistance vessels after ischemia and reperfusion. However, training did not preserve endothelial function of coronary resistance vessels, or myocardial contractile function, after ischemia and reperfusion.

Interactions between angiotensin II and nitric oxide during exercise in normal and heart failure rats.

We hypothesized that nitric oxide (NO) opposes ANG II-induced increases in arterial pressure and reductions in renal, splanchnic, and skeletal muscle vascular conductance during dynamic exercise in normal and heart failure rats. Regional blood flow and vascular conductance were measured during treadmill running before (unblocked exercise) and after 1) ANG II AT(1)-receptor blockade (losartan, 20 mg/kg ia), 2) NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME); 10 mg/kg ia], or 3) ANG II AT(1)-receptor blockade + NOS inhibition (combined blockade). Renal conductance during unblocked exercise (4.79 +/- 0.31 ml x 100 g(-1) x min(-1) x mmHg(-1)) was increased after ANG II AT(1)-receptor blockade (6.53 +/- 0.51 ml x 100 g(-1) x min(-1) x mmHg(-1)) and decreased by NOS inhibition (2.12 +/- 0.20 ml x 100 g(-1) x min(-1) x mmHg(-1)) and combined inhibition (3.96 +/- 0.57 ml x 100 g(-1) x min(-1) x mmHg(-1); all P < 0.05 vs. unblocked). In heart failure rats, renal conductance during unblocked exercise (5.50 +/- 0.66 ml x 100 g(-1) x min(-1) x mmHg(-1)) was increased by ANG II AT(1)-receptor blockade (8.48 +/- 0.83 ml x 100 g(-1) x min(-1) x mmHg(-1)) and decreased by NOS inhibition (2.68 +/- 0.22 ml x 100 g(-1) x min(-1) x mmHg(-1); both P < 0.05 vs. unblocked), but it was unaltered during combined inhibition (4.65 +/- 0.51 ml x 100 g(-1) x min(-1) x mmHg(-1)). Because our findings during combined blockade could be predicted from the independent actions of NO and ANG II, no interaction was apparent between these two substances in control or heart failure animals. In skeletal muscle, L-NAME-induced reductions in conductance, compared with unblocked exercise (P < 0.05), were abolished during combined inhibition in heart failure but not in control rats. These observations suggest that ANG II causes vasoconstriction in skeletal muscle that is masked by NO-evoked dilation in animals with heart failure. Because reductions in vascular conductance between unblocked exercise and combined inhibition were less than would be predicted from the independent actions of NO and ANG II, an interaction exists between these two substances in heart failure rats. L-NAME-induced increases in arterial pressure during treadmill running were attenuated (P < 0.05) similarly in both groups by combined inhibition. These findings indicate that NO opposes ANG II-induced increases in arterial pressure and in renal and skeletal muscle resistance during dynamic exercise.

Regional blood flow responses to acute ANG II infusion: effects of nitric oxide synthase inhibition.

We hypothesized that nitric oxide (NO) opposes regional vasoconstriction caused by acute angiotensin II (ANG II) infusion in conscious rats. Mean arterial pressure (MAP), blood flow, and vascular conductance (regional blood flow/ MAP; ml/min/100 g/mm Hg) were measured and/or calculated before and at 2 min of ANG II infusion (0.05 or 1 microg/kg/min, i.a.) in the absence and presence of NO synthase (NOS) inhibition [N(G)-nitro-L-arginine methyl ester (L-NAME), 0.25 or 1 mg/kg, i.a.]. ANG II reduced stomach and hindlimb conductance only after NOS inhibition. For example, whereas 0.05 microg/kg/min ANG II did not attenuate conductance in the stomach (i.e., 1.04+/-0.08 to 0.93+/-0.12 ml/min/100 g/mm Hg), this variable was reduced (i.e., 0.57+/-0.14 to 0.34-/+0.05 ml/min/100 g/mm Hg; p < 0.05) when ANG II was infused after 0.25 mg/kg L-NAME. In addition, whereas hindlimb conductance was similar before and after administering 1 microg/kg/min ANG II (i.e., 0.13+/-0.01 and 0.09+/-0.02, respectively), this variable was reduced (i.e., 0.07+/-0.01 and 0.02+/-0.00, respectively; p < 0.05) when ANG II was infused after 1 mg/kg L-NAME. These findings indicate that NO opposes ANG II-induced vasoconstriction in the stomach and hindlimb. In contrast, whereas both doses of ANG II decreased (p < 0.05) vascular conductance in the kidneys and small and large intestine regardless of whether NOS inhibition was present, absolute vascular conductance was lower (p < 0.05) after L-NAME. For example, 1 microg/kg ANG II reduced renal conductance from 3.34+/-0.31 to 1.22+/-0.14 (p < 0.05). After 1 mg/kg L-NAME, renal conductance decreased from 1.39+/-0.18 to 0.72+/-0.16 (p < 0.05) during ANG II administration. Therefore the constrictor effects of NOS inhibition and ANG II are additive in these circulations. Taken together, our results indicate that the ability of NO to oppose ANG II-induced constriction is not homogeneous among regional circulations.

Effects of caffeine on blood pressure, heart rate, and forearm blood flow during dynamic leg exercise.

This study examined the acute effects of caffeine on the cardiovascular system during dynamic leg exercise. Ten trained, caffeine-naive cyclists (7 women and 3 men) were studied at rest and during bicycle ergometry before and after the ingestion of 6 mg/kg caffeine or 6 mg/kg fructose (placebo) with 250 ml of water. After consumption of caffeine or placebo, subjects either rested for 100 min (rest protocol) or rested for 45 min followed by 55 min of cycle ergometry at 65% of maximal oxygen consumption (exercise protocol). Measurement of mean arterial pressure (MAP), forearm blood flow (FBF), heart rate, skin temperature, and rectal temperature and calculation of forearm vascular conductance (FVC) were made at baseline and at 20-min intervals. Plasma ANG II was measured at baseline and at 60 min postingestion in the two exercise protocols. Before exercise, caffeine increased both systolic blood pressure (17%) and MAP (11%) without affecting FBF or FVC. During dynamic exercise, caffeine attenuated the increase in FBF (53%) and FVC (50%) and accentuated exercise-induced increases in ANG II (44%). Systolic blood pressure and MAP were also higher during exercise plus caffeine; however, these increases were secondary to the effects of caffeine on resting blood pressure. No significant differences were observed in heart rate, skin temperature, or rectal temperature. These findings indicate that caffeine can alter the cardiovascular response to dynamic exercise in a manner that may modify regional blood flow and conductance.

Vasopressin acts in the area postrema to attenuate the exercise pressor reflex in anesthetized cats.

Circulating arginine vasopressin (AVP) can enhance baroreflex function via its action in the area postrema (AP). We tested the hypothesis that AVP acts in the AP to enhance baroreflex function during static contraction and, in turn, attenuates the exercise pressor reflex. Thus mean arterial blood pressure (n = 9) and heart rate (HR) (n = 9) during 30 s of electrically stimulated hindlimb contraction were compared before and after bilateral microinjections of 200 nl of the AVP V1-receptor antagonist d(CH2)5Tyr(Me)-AVP (V1x) (1 ng/nl) into the AP of the anesthetized cat. This protocol was repeated in three other cats in which sinoaortic denervation (SAD) was performed before any intervention. Injection of V1x into the AP had no effect on baseline blood pressure or HR. However, pressor and HR responses to static contraction were augmented by 44 +/- 10 and 29 +/- 9%, respectively. Static contraction also increased plasma AVP from 15.9 +/- 2.0 to 25.5 +/- 3.4 pg/ml. In the SAD cats, microinjection of V1x had no effect on contraction-induced increases in blood pressure or HR. These results suggest that baroreflex opposition of the reflex cardiovascular response to static contraction is enhanced by the action of AVP in the AP.

Effect of autonomic blockade on power spectrum of heart rate variability during exercise.

To validate power spectral analysis of heart rate variability (HRV) as an autonomic indicator during exercise, ten males performed four identical progressive cycling tests during infusions of saline, esmolol (beta 1-blocker), glycopyrrolate (muscarinic blocker), or both drugs. Power spectra were constructed from the recorded electrocardiogram by Fourier algorithm and integrated for low-frequency power (LF) and high-frequency power (HF). Four different LF bands (0.004-0.1, 0.004-0.15, 0.05-0.1, and 0.05-0.15 Hz) and two different HF bands (0.1-1.0 and 0.15-1.0 Hz) were evaluated. The parasympathetic index, HF, decreased exponentially with workload and was attenuated by glycopyrrolate and combined treatments with both HF frequency bands measured. Whereas some sympathetic indexes (LF/total power and LF/HF) did reflect expected increases in sympathetic nerve activity associated with progressive increases in work intensity, none of the measured increases responded appropriately to autonomic blockade. It is concluded that HRV is a valid technique for noninvasive measurement of parasympathetic tone during exercise, but its validity as a measure of sympathetic tone during exercise is equivocal.

The power athlete.

A number of normal daily and athletic activities require isometric or static exercise. Sports such as weight lifting and other high-resistance activities are used by power athletes to gain strength and skeletal muscle bulk. Static exercise, the predominant activity used in power training, significantly increases blood pressure, heart rate, myocardial contractility, and cardiac output. These changes occur in response to central neural irradiation, called central command, as well as a reflex originating from statically contracting muscle. Studies have demonstrated that blood pressure appears to be the regulated variable, presumably because the increased pressure provides blood flow into muscles whose arterial inflow is reduced as a result of increases in intramuscular pressure created by contraction. Thus, static exercise is characterized by a pressure load on the heart and can be differentiated from the hemodynamic response to dynamic (isotonic) exercise, which involves a volume load to the heart. Physical training with static exercise (i.e., power training) leads to concentric cardiac (particularly left ventricular) hypertrophy, whereas training with dynamic exercise leads to eccentric hypertrophy. The magnitude of cardiac hypertrophy is much less in athletes training with static than dynamic exercise. Neither systolic nor diastolic function is altered by the hypertrophic process associated with static exercise training. Many of the energy requirements for static exercise, particularly during more severe levels of exercise, are met by anaerobic glycolysis because the contracting muscle becomes comes deprived of blood flow. Power athletes, training with repetitive static exercise, derive little benefit from an increase in oxygen transport capacity, so that maximal oxygen consumption is increased only minimally or not at all. Peripheral cardiovascular adaptations also can occur in response to training with static exercise. Although the studies are controversial, these adaptations include modest decreases in resting blood pressure, reduced increases in blood pressure and sympathetic nerve activity during a given workload, enhanced baroreflex function, increases in muscle capillary-to-fiber ratio, possible improvements in lipid and lipoprotein profiles, and increases in glucose and insulin responsiveness. Some of these adaptations can occur in cardiac or hypertensive patients with no concomitant cardiovascular complications. In both healthy individuals and those with cardiovascular disease, the manner in which resistance training is performed may dictate the extent to which these adjustments take place. Specifically, training that involves frequent repetitions of moderate weight (and hence contains dynamic components) seems to produce the most beneficial results.

Area postrema-induced inhibition of the exercise pressor reflex.

The exercise pressor reflex is opposed by the arterial baroreflex, and circulating peptides may act in the area postrema to enhance this inhibition. Therefore, we tested the hypothesis that the area postrema exerts an inhibitory effect on this reflex. Consequently, in six alpha-chloralose-anesthetized cats, blood pressure and heart rate responses to 30 s of electrically stimulated hindlimb contraction were compared before and after thermal coagulation of the area postrema. In six other cats, the same contraction-induced cardiovascular responses were assessed before and after chemical lesion of the area postrema using kainic acid (214 +/- 9 nl, 2.5-5 mM). Thermal lesion of the area postrema augmented blood pressure and heart rate responses to contraction from 29 +/- 5 to 47 +/- 7 mmHg (P < 0.05) and from 8 +/- 2 to 14 +/- 2 beats/min (P < 0.05), respectively. Chemical lesion of the area postrema enhanced contraction-evoked blood pressure (30 +/- 7 vs. 47 +/- 6 mmHg, P < 0.05) and heart rate (12 +/- 4 vs. 17 +/- 4 beats/min, P < 0.05) responses. These data suggest that the area postrema attenuates the exercise pressor reflex, possibly through the actions of circulating peptides on baroreflex function.

Production of hydroxyl radicals in contracting skeletal muscle of cats.

Reactive oxygen species increase during exhaustive contraction of skeletal muscle, but characterization of the specific species involved and their rates of production during nonexhaustive muscle contraction have not been investigated. We hypothesized that the production rate of hydroxyl radical (.OH) increases in contracting muscle and that this rate is attenuated by pretreatment with deferoxamine (Def) or dimethylthiourea (DMTU). We measured the rate of production of .OH before, during, and after 5 min of intermittent static contraction of the triceps surae muscles in cats (n = 6) using the formation of p-, m-, and o-tyrosines by hydroxylation of phenylalanine. L-Phenylalanine (30 mg/kg i.v.) was administered to each animal 3 min before contraction. Blood samples were collected from the popliteal vein 1 min before contraction; 1, 3, and 4.5 min during contraction; and 1 min after contraction. During and after contraction, the cumulative production rates of p-, m-, and o-tyrosines were elevated by 42.84 +/- 5.41, 0.25 +/- 0.04, and 0.21 +/- 0.03 nmol.min-1.g-1, respectively, compared with noncontracting triceps surae muscles. Pretreatment with Def (10 mg/kg i.v.; n = 5) or DMTU (10 mg/kg i.v.; n = 4) decreased the cumulative rates of production of p-, m-, and o-tyrosines during and after contraction. Additionally, the rate of tyrosine production increased in proportion to the percentage of maximal tension developed by the triceps surae muscles. These results directly demonstrate that .OH is produced in vivo in the skeletal muscle of cats during intermittent static contraction and that production can occur before the onset of fatigue.

Reactive oxygen species modify reflex cardiovascular responses to static contraction.

Reactive oxygen species can reflexly activate the cardiovascular system through stimulation of abdominal visceral afferents. The mechanism appears to involve hydroxyl radicals. We tested the hypothesis that reactive oxygen species contribute to the reflex cardiovascular response to static muscle contraction (i.e., the exercise pressor reflex). Thus blood pressure and heart rate responses to 5 min of intermittent electrically stimulated static contraction of the triceps surae muscles (15 s on, 15 s off) in anesthetized cats were compared before and after intravenous administration of the free radical scavengers dimethylthiourea (DMTU; 10 mg/kg; n = 8) or deferoxamine (Def; 10 mg/kg; n = 15). The contraction-induced pressor response was augmented from 51 +/- 6 to 61 +/- 7 mmHg after treatment with DMTU (P < 0.05) and from 44 +/- 8 to 58 +/- 8 mmHg after administration of Def (P < 0.05). Corresponding heart rate responses were not affected by either drug. Because this DMTU- or Def-induced augmentation of the exercise pressor reflex may have been due to a reduction in free radical-evoked vasodilation in the contracting skeletal muscle, popliteal artery blood velocity was measured with a Doppler flow transducer before and during contraction in the absence and presence of Def (n = 8). Blood velocity during contraction was not altered by Def (16 +/- 5 vs. 24 +/- 6 cm/s). These data suggest that reactive oxygen species exert an inhibitory effect on the exercise pressor reflex that is not associated with their local vasodilator properties. This response is opposite to that observed during stimulation of visceral afferents by reactive oxygen species.

Endogenous bradykinin in the thoracic spinal cord contributes to the exercise pressor reflex.

This investigation tested the hypothesis that bradykinin causes excitatory effects in the thoracic spinal cord that augment the exercise pressor reflex. Thus we performed 30 s of electrically stimulated static contraction of the hindlimb in the anesthetized cat (alpha-chloralose) to provoke reflex-induced increases in mean arterial pressure, maximal rate of rise of left ventricular pressure (dP/dt), and heart rate (i.e., the exercise pressor reflex). These three responses were compared before and 15 min after intrathecal injection of 2 micrograms (n = 3), 10 micrograms (n = 6), or 50 micrograms (n = 3) of the selective bradykinin B2- receptor antagonist HOE-140 into the thoracic spinal cord or 10 micrograms of this antagonist into the lumbar (n = 3) spinal cord. In three of the six cats in which 10 micrograms of HOE-140 were injected into the thoracic spinal cord, an additional contraction was performed 60-90 min after treatment. The 2-microgram dose of HOE-140 had no effect on the exercise pressor reflex. Injection of 10 micrograms of this antagonist into the thoracic spinal cord reduced the contraction-evoked pressor, maximal dP/dt, and heart rate responses by 49 +/-7, 58 +/- 4, and 64 +/- 13%, respectively (P < 0.05). Fifty micrograms of HOE-140 failed to attenuate these responses further. In the three cats in which an additional contraction was performed 60-90 min after treatment with 10 micrograms of the antagonist, blood pressure and dP/dt responses had returned, in part, toward initial values. Neither intravenous (n = 3) nor intrathecal injection of 10 micrograms of HOE-140 into the lumbar spinal cord had any effect on the contraction-induced cardiovascular responses. Thoracic injection of 50-200 ng of bradykinin provoked a pressor response of 26 +/- 5 mmHg that was abolished by a similar injection of 10 micrograms of HOE-140. These data suggest that endogenous bradykinin contributes to the exercise pressor reflex by an excitatory action in the thoracic spinal cord.

Effects of angiotensin II receptor blockade during exercise: comparison of losartan and saralasin.

Previous studies indicate that angiotensin II (ANG II) plays a minor role in the hemodynamic responses during dynamic exercise. However, nonspecific effects associated with methods used to block its production [e.g., angiotensin-converting enzyme (ACE) inhibitors] or receptors (e.g., saralasin) may have contributed to these findings. Losartan is a nonpeptide ANG II receptor antagonist that is devoid of such nonspecific effects. We hypothesized that the contribution of ANG II to the cardiovascular response to dynamic exercise is characterized more precisely with losartan than with saralasin. On separate days, 6 miniswine performed treadmill running at 80% of their maximal heart rate (HR) reserve (HRR) in the presence of vehicle (0.9% saline), saralasin (10 or 20 micrograms/kg/min intraleft arterially, i.a.), or losartan (15 or 20 mg/kg i.a.). Cardiac output (CO), HR, and myocardial contractility were similar among all exercise conditions. As compared with the vehicle, losartan decreased mean arterial pressure (MAP) and systemic vascular resistance (SVR) during exercise, whereas no differences occurred between the vehicle and saralasin conditions. Both receptor antagonists increased blood flow and/or decreased vascular resistance during exercise in the myocardium, stomach, small intestine, and colon. As compared with that during treadmill running with vehicle infusion, renal blood flow (RBF) was increased by losartan and decreased by saralasin. We conclude that the contribution of ANG II to the cardiovascular response to dynamic exercise is demonstrated more clearly with losartan than with saralasin.

Hemodynamic and regional blood flow responses to nicotine at rest and during exercise.

We hypothesized that nicotine compromises cardiovascular responses to dynamic exercise. Hemodynamic variables were measured in conscious miniswine before and at 2 min of nicotine infusion (20 micrograms.kg-1.min-1; i.a.; N = 6) during resting conditions. Mean arterial pressure elevations (MAP; 14%) and plasma nicotine concentrations (49 +/- 7 ng.ml-1) were similar to those elicited by cigarette smoking in humans. In addition, nicotine increased systemic vascular resistance (SVR; 56%), the heart rate x systolic blood pressure product (RPP; 11%), and regional vascular resistance in the left-ventricular, renal, and splanchnic circulations, while cardiac output decreased (CO; 23%) and skeletal muscle blood flow and vascular resistance were unaffected. Plasma norepinephrine and epinephrine increased by approximately 30% and 90%, respectively. On separate days, the same hemodynamic responses were measured before and at 20 min of treadmill running during vehicle or nicotine infusion for the last 2 min of exercise (N = 10). Nicotine increased MAP (6%), SVR (14%), and RPP (3%), and elevated vascular resistance in the proximal colon and pancreas. Moreover, compared to exercise + vehicle, norepinephrine and epinephrine increased by approximately 13% and 24%, respectively, during exercise + nicotine infusion. These findings suggest that the detrimental effects of nicotine observed at rest are minimized during exercise. Nicotine's effects may be reduced during exercise by competition from local vasodilators in the heart and active musculature, and/or by differing activation of sympathetic nerve activity.