Citations

We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to ∼20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with N G-monomethyl-l-arginine (l-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with l-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, butl-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereasl-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation thatl-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.

Joyner, Michael J., and Niki M. Dietz.Nitric oxide and vasodilation in human limbs. J. Appl. Physiol. 83(6): 1785–1796, 1997.—Both the skeletal muscle and skin of humans possess remarkable abilities to vasodilate. Marked vasodilation can be seen in these vascular beds in response to a variety of common physiological stimuli. These stimuli include reactive hyperemia (skin and muscle), exercise hyperemia (muscle), mental stress (muscle), and whole body heating (skin). The physiological mechanisms that cause vasodilation in response to these stimuli are poorly understood, and the substance(s) responsible for it remain unclear. In this context, recent attention has been focused on the possible contribution of nitric oxide (NO) to the regulation of hyperemic responses in human skin and skeletal muscle. The emerging picture is that NO is not an essential component of the dilator response seen during reactive hyperemia. However, it does appear that NO may play a modest role in exercise hyperemia. NO appears to play a major role in the skeletal muscle vasodilation seen in response to mental stress in humans. Preliminary evidence also indicates that NO is not essential for the normal dilator responses observed in the cutaneous circulation during body heating in humans, but this issue needs further study. There are a number of possible mechanisms that might mediate NO release in humans, and the role of these mechanisms in the various hyperemic responses is also poorly understood. The role of altered NO-mediated vasodilation in some disease states is also discussed. Whereas NO is a potent vasodilating substance, the actions of NO alone do not explain a variety of poorly understood vasodilator mechanisms in conscious humans. Much work remains for those interested in the role of NO in the regulation of blood flow to the skin and skeletal muscle of humans.

We sought to investigate further the roles of sweating, ACh spillover, and nitric oxide (NO) in the neurally mediated cutaneous vasodilation during body heating in humans. Six subjects were heated with a water-perfused suit while cutaneous blood flow was measured with a laser-Doppler flowmeter. After a rise in core temperature (1.0 ± 0.1°C) and the establishment of cutaneous vasodilation, atropine and subsequently the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) were given to the forearm via a brachial artery catheter. After atropine infusion, cutaneous vascular conductance (CVC) remained constant in five of six subjects, whereasl-NAME administration blunted the rise in CVC in three of six subjects. A subsequent set of studies using intradermal microdialysis probes to selectively deliver drugs into forearm skin confirmed that atropine did not affect CVC. However, perfusion ofl-NAME resulted in a significant decrease in CVC (37 ± 4%, P < 0.05). The results indicate that neither sweating nor NO release via muscarinic receptor activation is essential to sustain cutaneous dilation during heating in humans.

Three anesthetics (pentobarbital, halothane, and isoflurane) were studied in six mongrel dogs to systematically compare their effects on chest wall function during spontaneous breathing. Each dog received each anesthetic on separate occasions. Electrical activities of several respiratory muscles were measured with chronically implanted electrodes, and chest wall motion was assessed by high-speed three-dimensional computed tomography scanning. Phasic expiratory muscle activity was markedly depressed by volatile anesthetics halothane and isoflurane compared with pentobarbital. In contrast, inspiratory activity in parasternal intercostal muscles was relatively well preserved during anesthesia with these volatile agents. The contribution of expiratory muscles to tidal volume was diminished during halothane and isoflurane compared with pentobarbital anesthesia. As anesthesia was deepened, expiratory muscle activity was unchanged during pentobarbital anesthesia, enhanced in some dogs during isoflurane anesthesia, and remained absent during halothane anesthesia. Activity in parasternal intercostal muscle was depressed as inspired concentration of halothane or isoflurane was increased, whereas diaphragmatic activity was unchanged. Depression of expiratory muscle activity by halothane persisted when breathing was stimulated by positive end-expiratory pressure, with significant mechanical consequences for chest wall configuration. Many of these findings are in contrast with previous observations in humans and suggest that the dog is not a suitable model for the study of the effects of anesthetic drugs on the pattern of human respiratory muscle activity.

Dietz, Niki M., John R. Halliwill, John M. Spielmann, Lori A. Lawler, Bettina G. Papouchado, Tamara J. Eickhoff, and Michael J. Joyner. Sympathetic withdrawal and forearm vasodilation during vasovagal syncope in humans. J. Appl. Physiol. 82(6): 1785–1793, 1997.—Our aim was to determine whether sympathetic withdrawal alone can account for the profound forearm vasodilation that occurs during syncope in humans. We also determined whether either vasodilating β2-adrenergic receptors or nitric oxide (NO) contributes to this dilation. Forearm blood flow was measured bilaterally in healthy volunteers ( n = 10) by using plethysmography during two bouts of graded lower body negative pressure (LBNP) to syncope. In one forearm, drugs were infused via a brachial artery catheter while the other forearm served as a control. In the control arm, forearm vascular resistance (FVR) increased from 77 ± 7 units at baseline to 191 ± 36 units with −40 mmHg of LBNP ( P < 0.05). Mean arterial pressure fell from 94 ± 2 to 47 ± 4 mmHg just before syncope, and all subjects demonstrated sudden bradycardia at the time of syncope. At the onset of syncope, there was sudden vasodilation and FVR fell to 26 ± 6 units ( P < 0.05 vs. baseline). When the experimental forearm was treated with bretylium, phentolamine, and propranolol, baseline FVR fell to 26 ± 2 units, the vasoconstriction during LBNP was absent, and FVR fell further to 16 ± 1 units at syncope ( P < 0.05 vs. baseline). During the second trial of LBNP, mean arterial pressure again fell to 47 ± 4 mmHg and bradycardia was again observed. Treatment of the experimental forearm with the NO synthase inhibitor NG-monomethyl-l-arginine in addition to bretylium, phentolamine, and propranolol significantly increased baseline FVR to 65 ± 5 units but did not prevent the marked forearm vasodilation during syncope (FVR = 24 ± 4 vs. 29 ± 8 units in the control forearm). These data suggest that the profound vasodilation observed in the human forearm during syncope is not mediated solely by sympathetic withdrawal and also suggest that neither β2-adrenergic-receptor-mediated vasodilation nor NO is essential to observe this response.

We previously reported that epinephrine stimulates leg free fatty acid (FFA) release in men but not in women. The present studies were conducted to determine whether the same is true during exercise. Six men and six women bicycled for 90 min at 45% of peak O2 consumption, during which time systemic and leg FFA kinetics ([9,10-3H]palmitate) were measured. The catecholamine and hormonal responses to exercise were not different in men and women. The baseline systemic and leg palmitate release was 94 ± 15 vs. 114 ± 5 μmol/min and 16 ± 2 and 20 ± 3 μmol/min, respectively, in men and women [ P = nonsignificant (NS)]. Systemic and leg palmitate release increased (both P < 0.001) to 251 ± 18 vs. 212 ± 16 μmol/min and 73 ± 19 vs. 80 ± 12 μmol/min in men and women, respectively, during the last 30 min of exercise ( P = NS, men vs. women). We conclude that the systemic and leg adipose tissue lipolytic response to exercise is not different in nonobese men and women.

Engelke, Keith A., John R. Halliwill, David N. Proctor, Niki M. Dietz, and Michael J. Joyner. Contribution of nitric oxide and prostaglandins to reactive hyperemia in the human forearm. J. Appl. Physiol. 81(4): 1807–1814, 1996.—We investigated the separate and combined contributions of nitric oxide (NO) and vasodilating prostaglandins as mediators of reactive hyperemia in the human forearm. Forearm blood flow (FBF) was measured with venous occlusion plethysmography after 5 min of ischemia. In one protocol ( n = 12), measurements were made before and after intra-arterial administration of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) to one forearm. In a separate protocol ( n = 7), measurements were made before and after systemic administration of the cyclooxygenase inhibitor ibuprofen and again afterl-NMMA.l-NMMA reduced baseline FBF at rest (2.7 ± 0.4 to 1.6 ± 0.2 ml ⋅ 100 ml−1⋅ min−1; P < 0.05) and had a modest effect on peak forearm vascular conductance and flow (forearm vascular conductance = 31.1 ± 3.1 vs. 25.7 ± 2.5 ml ⋅ min−1⋅ 100 ml forearm−1⋅ 100 mmHg of perfusion pressure−1⋅ min−1, P < 0.05; FBF = 26.6 ± 2.9 vs. 22.8 ± 2.6 ml ⋅ 100 ml−1⋅ min−1, P = 0.055). Total excess flow above baseline during reactive hyperemia was unaffected byl-NMMA (14.3 ± 3.0 vs. 13.1 ± 2.3 ml/100 ml; P < 0.05). Ibuprofen did not change FBF at rest, reduced peak FBF from 27.6 ± 1.9 to 20.3 ± 2.7 ml ⋅ 100 ml−1⋅ min−1( P < 0.05), but had no effect on total excess flow above baseline. Infusion ofl-NMMA after ibuprofen reduced FBF at rest by 40%, had no effect on peak flow, but reduced total excess flow above baseline from 12.0 ± 2.5 to 7.6 ± 1.3 ml/100 ml ( P < 0.05). These data demonstrate that NO synthase inhibition has a modest effect on peak vasodilation during reactive hyperemia but plays a minimal role later. Prostaglandins appear to be important determinants of peak flow. The effects of NO synthase inhibition during reactive hyperemia may also be potentiated by concurrent cyclooxygenase inhibition.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

Proctor, David N., and Michael J. Joyner. Skeletal muscle mass and the reduction ofV˙o 2 max in trained older subjects. J. Appl. Physiol.82(5): 1411–1415, 1997.—The role of skeletal muscle mass in the age-associated decline in maximal O 2 uptake (V˙o 2 max ) is poorly defined because of confounding changes in muscle oxidative capacity and in body fat and the difficulty of quantifying active muscle mass during exercise. We attempted to clarify these issues by examining the relationship between several indexes of muscle mass, as estimated by using dual-energy X-ray absorptiometry and treadmillV˙o 2 max in 32 chronically endurance-trained subjects from four groups ( n = 8/group): young men (20–30 yr), older men (56–72 yr), young women (19–31 yr), and older women (51–72 yr).V˙o 2 max per kilogram body mass was 26 and 22% lower in the older men (45.9 vs. 62.0 ml ⋅ kg −1 ⋅ min −1 ) and older women (40.0 vs. 51.5 ml ⋅ kg −1 ⋅ min −1 ). These age differences were reduced to 14 and 13%, respectively, whenV˙o 2 max was expressed per kilogram of appendicular muscle. When appropriately adjusted for age and gender differences in appendicular muscle mass by analysis of covariance, whole bodyV˙o 2 max was 0.50 ± 0.09 l/min less ( P < 0.001) in the older subjects. This effect was similar in both genders. These findings suggest that the reducedV˙o 2 max seen in highly trained older men and women relative to their younger counterparts is due, in part, to a reduced aerobic capacity per kilogram of active muscle independent of age-associated changes in body composition, i.e., replacement of muscle tissue by fat. Because skeletal muscle adaptations to endurance training can be well maintained in older subjects, the reduced aerobic capacity per kilogram of muscle likely results from age-associated reductions in maximal O 2 delivery (cardiac output and/or muscle blood flow).