Is tonic sympathetic vasoconstriction increased in the skeletal muscle vasculature of aged canines?

We tested the hypothesis that tonic adrenergic and nonadrenergic receptor-mediated sympathetic vasoconstriction would increase at rest and during exercise with advancing age. Young (n = 6; 22 ± 1 mo; means ± SE) and old (n = 6; 118 ± 9 mo) beagles were studied. Selective antagonists for alpha-1, alpha-2, neuropeptide Y (NPY), and purinergic (P(2x)) receptors were infused at rest and during treadmill running at 2.5 mph and 4 mph with 2.5% grade. Prazosin produced similar increases in vascular conductance in young and old beagles at rest (Young: 158 ± 34%; Old: 98 ± 19%) and during exercise at 2.5 mph (Young: 80 ± 10%; Old: 58 ± 12%) and 4 mph and 2.5% grade (Young: 57 ± 5%; Old: 26 ± 4%). Rauwolscine caused similar (P > 0.05) increases in vascular conductance in old compared with young dogs at rest (Young: 119 ± 25%; Old: 64 ± 22%) and at 2.5 mph (Young: 86 ± 13%; Old: 60 ± 7%) and 4 mph with 2.5% grade (Young: 61 ± 5%; Old: 43 ± 7%). N2-(diphenylacetyl)-N-[4-hydroxyphenyl)methyl]-d-arginine amide (BIBP) caused a smaller increase (P < 0.05) in vascular conductance in old compared with young dogs at rest (Young: 179 ± 44%; Old: 91 ± 22%), whereas similar increases (P > 0.05) of experimental limb vascular conductance in young and old dogs occurred following BIBP during exercise at 2.5 mph (Young: 56 ± 16%; Old: 50 ± 12%) and 4 mph and 2.5% grade (Young: 45 ± 10%; Old: 25 ± 7%). Pyridoxal-phosphate-6-azophenyl-2'-4'-disulfonic acid infusion produced a larger increase in vascular conductance in old compared with young beagles at rest (Young: 88 ± 14%; Old: 191 ± 58%), whereas similar increases were observed at 2.5 mph (Young: 47 ± 18%; Old: 31 ± 11%) and 4 mph with 2.5% grade (Young: 26 ± 13%; Old: -18 ± 8%). At rest, NPY receptor-mediated restraint of skeletal muscle blood flow was reduced with advancing age, whereas P(2x) receptor-mediated restraint of skeletal muscle blood flow was increased. During exercise, the magnitude of adrenergic and nonadrenergic sympathetic vasoconstriction was not different between young and old dogs. Overall, these data demonstrate that adrenergic receptor-mediated vasoconstriction was not elevated at rest, but nonadrenergic sympathetic vasoconstriction was altered under basal conditions in aged beagles.

Absence of flow-mediated vasodilation in the rabbit femoral artery.

The purpose of this study was to determine if there is flow-mediated vasodilation of the femoral artery in response to progressive increases in flow within a physiological range observed in the in vivo experiments. Femoral artery blood flow was determined in conscious rabbits (n = 5) using chronically implanted flowprobes. Resting blood flow was 8.3 +/- 0.6 ml/min and increased to 39.9 +/- 5.4 ml/min during high intensity exercise. Femoral arteries (n = 12, 1705 +/- 43 microm outer diameter) harvested from a separate group of rabbits were mounted on cannulas and diameter was continuously monitored by video system. Functional integrity of the endothelium was tested with acetylcholine. The arteries were set at a transmural pressure of 100 mm Hg and preconstricted with phenylephrine to 73 +/- 3% of initial diameter. Using a roller pump with pressure held constant, the arteries were perfused intraluminally with warmed, oxygenated Krebs' solution (pH = 7.4) over a physiological range of flows up to 35 ml/min. As flow increased from 5 ml/min to 35 ml/min, diameter decreased significantly (p < 0.05) from 1285 +/- 58 microm to 1100 +/- 49 microm. Thus, in vessels with a functional endothelium, increasing intraluminal flow over a physiological range of flows produced constriction, not dilation. Based on these results, it seems unlikely that flow-mediated vasodilation in the rabbit femoral artery contributes to exercise hyperemia.

Mixed venous blood gases are superior to arterial blood gases in assessing acid-base status and oxygenation during acute cardiac tamponade in dogs.

Recent reports using anesthetized ventilator-dependent animal models, have suggested that in certain shock states, a disparity exists between arterial and mixed venous blood gases with regard to acid-base status and oxygenation. In a chronically instrumented unanesthetized canine model of acute cardiac tamponade breathing room air, we studied the effect of a graded decline in cardiac output on arterial and mixed venous pH, PCO2, and PO2. Cardiac tamponade resulted in a profound arterial respiratory alkalosis, whereas mixed venous pH, PCO2, and calculated serum bicarbonate levels remained relatively unchanged. As intrapericardial pressure increased and cardiac output declined, the difference between arterial and mixed venous PCO2 progressively increased. Further, whereas arterial oxygenation improved as cardiac output declined, mixed venous oxygenation steadily worsened. This disparity began early in cardiac tamponade (reductions in cardiac output of 20-40%) long before arterial blood pressure began to fall and progressively worsened as hemodynamic deterioration and lactic acidosis developed. Our findings are consistent with the hypothesis that a reduction in blood flow, resulting in decreased CO2 delivery to the lungs, is the primary mechanism responsible for the difference in pH and PCO2 observed between arterial and mixed venous blood. In this conscious, spontaneously breathing animal model, mixed venous blood gases thus are superior to arterial blood gases in assessing acid-base status and oxygenation, even early in acute cardiac tamponade when the decline in cardiac output is in the range of 20 to 40% and arterial blood pressure has not changed significantly.

Effect of head-out water immersion on cardiorespiratory response to dynamic exercise.

Head-out water immersion is known to produce several cardiopulmonary adjustments at rest due to a cephalad shift in blood volume. The purpose of this study was to determine the effect of head-out water immersion on the cardiorespiratory response to graded dynamic exercise. Nineteen healthy middle-aged men performed upright cycling exercise at 40, 60 and 80% of maximal oxygen consumption on land and in water (31.0 +/- 1.0 degrees C) to the shoulders. Cardiac output (measured by the carbon dioxide rebreathing technique) was significantly greater in water at 40 and 80% maximal oxygen consumption. Stroke volume was significantly elevated at all stages of exercise. Heart rate did not differ significantly at 40 and 60% maximal oxygen consumption but was significantly lower in water at 80% maximal oxygen consumption. Total ventilation did not differ significantly in water and on land at any stage of exercise. The results suggest that the central redistribution of blood volume with head-out water immersion leads to an increase in stroke volume. Because there is not a proportional decrease in heart rate with the elevated stroke volume, cardiac output is regulated at a higher level during upright exercise in water compared with that on land. In conclusion, there are serious limitations of available, prerecorded rhythm data bases for designing and testing of automatic external defibrillators. Performance can be adequately assessed only by extensive clinical tests, which seem mandatory for this new and important type of defibrillator.

Restricted postexercise pulmonary diffusion capacity does not impair maximal transport for O2.

We evaluated whether the postexercise reduction of pulmonary diffusion capacity for carbon monoxide (DLco) is influenced by a second bout of rowing and whether it affects arterial O2 tension during maximal exercise. After exercise, DLco was reduced [from a median of 37 (range of 30-44) to 34 (27-40) ml.min-1.mmHg-1; n = 21; P < 0.001], and both the membrane diffusion capacity [from 80 (58-139) to 68 (54-104) ml.min-1.mmHg-1] and the pulmonary capillary blood volume [from 88 (74-119) to 79 (61-121) ml; P < 0.01] were affected. A second bout of exercise did not influence DLco or membrane diffusion capacity (n = 7), but during both bouts arterial O2 tension was reduced [from 105 (91-110) to 91 (77-102) Torr; P < 0.001] and arterial O2 saturation decreased [from 0.98 (0.97-0.99) to 0.95 (0.86-0.96); P < 0.001]. Furosemide (iv) did not affect DLco (n = 7), suggesting that it was influenced by the central blood volume rather than by pulmonary edema.

Functional anatomy of the vagal innervation of the cervical trachea of the dog.

The canine cervical trachea has been used for numerous studies regarding the neural control of tracheal smooth muscle. The purpose of the present study was to determine whether there is lateral dominance by either the left or right vagal innervation of the canine cervical trachea. In anesthetized dogs, pressure in the cuff of the endotracheal tube was used as an index of smooth muscle tone in the trachea. After establishment of tracheal tone, as indicated by increased cuff pressure, either the right or left vagus nerve was sectioned followed by section of the contralateral vagus. Sectioning the right vagus first resulted in total loss of tone in the cervical trachea, whereas sectioning the left vagus first produced either a partial or no decrease in tracheal tone. After bilateral section of the vagi, cuff pressure was recorded during electrical stimulation of the rostral end of the right or left vagus. At the maximum current strength used, stimulation of the left vagus produced tracheal constriction that averaged 28.5% of the response to stimulation of the right vagus (9.0 +/- 1.8 and 31.6 +/- 2.5 mmHg, respectively). In conclusion, the musculature of cervical trachea in the dog appears to be predominantly controlled by vagal efferents in the right vagus nerve.

Dynamic exercise attenuates sympathetic responsiveness of canine vascular smooth muscle.

The phenomenon of reduced responsiveness of the skeletal muscle arterial vasculature to sympathetic activation during exercise (sympatholysis) remains controversial. The purpose of this study was to examine the vascular effects of sympathoactivation in dynamically exercising skeletal muscle. Mongrel dogs (19-24 kg) were instrumented chronically with transit-time ultrasonic flow probes on the external iliac arteries. After pretreatment with atropine (0.2 mg/kg), an intravenous bolus (4 microg/kg) of a nicotinic ganglion stimulant [1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)] was given at rest and during treadmill exercise at graded intensities. Administration of DMPP was associated with prompt reductions in iliac blood flow and increases in arterial pressure under all conditions. There were significant reductions (P < 0.05) in iliac vascular conductance of 58 +/- 4 (SE), 48 +/- 3, 36 +/- 5, and 16 +/- 3% at rest, 3 miles/h and 0% grade, 6 miles/h and 0% grade, and 6 miles/h and 15% grade, respectively. These data demonstrate that activation of postganglionic sympathetic nerves with DMPP caused vasoconstriction in the skeletal muscle vasculature at rest and during exercise. Additionally, the magnitude of vasoconstriction was inversely related to exercise intensity. These results support the concept of exercise sympatholysis.

Arterial hypocapnia during exercise in beagle dogs.

Previous investigators have assumed that during exercise there is a tight coupling of ventilation with CO2 delivery to the lungs such that arterial blood remains isocapnic. We measured arterial blood gases in a group of 10 beagle dogs in which arterial blood sampling could be accomplished via exteriorized carotid artery loops and in six of the same dogs following chronic pulmonary denervation. Samples were taken at rest, at 15-s intervals during the first minute of unrestrained treadmill exercise at 5.0 km/h, 0% grade, and then at 2 and 3 min at the same work load. Mean resting arterial PCO2 for the control dogs was 37.1 Torr. At the onset of exercise arterial PCO2 fell progressively to a nadir of 34.6 Torr during the 30- to 45-s sampling period. Samples at 2 and 3 min remained significantly hypocapnic (PCO2 = 34.8 Torr). The arterial PCO2 and pH responses to exercise in the lung-denervated dogs were not significantly different from those of the control dogs, although arterial PO2 was lower at rest and during exercise following denervation of the lungs. The arterial hypocapnia exhibited in intact beagle dogs at the onset of exercise persists into the steady state and suggests that there is not a tight coupling of ventilation with pulmonary CO2 delivery. The similarity of the response in lung-denervated dogs suggests that intrapulmonary receptors with afferents in the vagi are not the primary mediators of the ventilatory response to exercise.

Muscle chemoreflex increases renal sympathetic nerve activity during exercise.

Activation of the muscle chemoreflex increases sympathetic drive to skeletal muscle in humans. This study investigated whether activation of the muscle chemoreflex augments the renal sympathetic nerve activity (RSNA) response to dynamic exercise in rabbits. The muscle chemoreflex was evoked by hindlimb ischemia during exercise on a motorized treadmill. Seven New Zealand White rabbits performed a nonischemic control protocol and a hindlimb ischemia protocol in which terminal aortic blood flow (Qta) was reduced to 51 +/- 2% of preocclusion Qta by partial aortic occlusion after 1.5 min of exercise. Mean arterial pressure (MAP), heart rate, RSNA and Qta increased in response to exercise and were similar between trials during the first 1.5 min of exercise. In the control trial, Qta, MAP, and RSNA were stable at an elevated level through an additional 3.5 min of exercise. Hindlimb ischemia produced a potent pressor response that plateaued after 2.5 min (delta + 17 +/- 4 mmHg, where delta designates change). RSNA began to increase after 1.5 min of ischemic exercise and was significantly elevated relative to preocclusion RSNA at 2.5 (delta + 25 +/- 9%) and 3.5 (delta + 47 +/- 12%) min of occlusion. These results suggest that the muscle chemoreflex can augment sympathoexcitatory drive to the kidney during dynamic exercise.

Autonomic control of skeletal muscle vasodilation during exercise.

Despite extensive investigation, the control of blood flow during dynamic exercise is not fully understood. The purpose of this study was to determine whether beta-adrenergic or muscarinic receptors are involved in the vasodilation in exercising skeletal muscle. Six mongrel dogs were instrumented with ultrasonic flow probes on both external iliac arteries and with a catheter in a branch of one femoral artery. The dogs exercised on a treadmill at 6 miles/h while drugs were injected intra-arterially into one hindlimb. Isoproterenol (0.2 microg) or acetylcholine (1 microg) elicited increases in iliac blood flow of 89.8 +/- 14.4 and 95.6 +/- 17.4%, respectively, without affecting systemic blood pressure or blood flow in the contralateral iliac artery. Intra-arterial propranolol (1 mg) or atropine (500 microg) had no effect on iliac blood flow, although they abolished the isoproterenol and acetylcholine-induced increases in iliac blood flow. These data indicate that exogenous activation of beta-adrenergic or muscarinic receptors in the hindlimb vasculature increases blood flow to dynamically exercising muscle. More importantly, because neither propranolol nor atropine affected iliac blood flow, we conclude that beta-adrenergic and muscarinic receptors are not involved in the control of blood flow to skeletal muscle during moderate steady-state dynamic exercise in dogs.

Sympathetic vasoconstriction in active skeletal muscles during dynamic exercise.

Studies utilizing systemic administration of alpha-adrenergic antagonists have failed to demonstrate sympathetic vasoconstriction in working muscles during dynamic exercise. The purpose of this study was to examine the existence of active sympathetic vasoconstriction in working skeletal muscles by using selective intra-arterial blockade. Six mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and with a catheter in one femoral artery. All dogs ran on a motorized treadmill at three intensities on separate days. After 2 min, the selective alpha 1-adrenergic antagonist prazosin (0.1 mg) was infused as a bolus into the femoral artery catheter. At mild, moderate, and heavy workloads, there were immediate increases in iliac conductance of 76 +/- 7, 54 +/- 11, and 22 +/- 6% (mean +/- SE), respectively. Systemic blood pressure and blood flow in the contralateral iliac artery were unaffected. These results demonstrate that there is sympathetic vasoconstriction in active skeletal muscles even at high exercise intensities.

alpha1-adrenergic-receptor responsiveness in skeletal muscle during dynamic exercise.

Attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during dynamic exercise is controversial. One potential mechanism is a reduction in alpha1-adrenergic-receptor responsiveness. The purpose of this study was to examine alpha1-adrenergic-receptor-mediated vasoconstriction in resting and working skeletal muscles by using intra-arterial infusions of a selective agonist. Seven mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. A selective alpha1-adrenergic-receptor agonist (phenylephrine) was infused as a bolus into the femoral artery catheter at rest and during exercise. All dogs ran on a motorized treadmill at two exercise intensities (3 and 6 miles/h). Intra-arterial infusions of the same effective concentration of phenylephrine elicited reductions in vascular conductance of 76 +/- 4, 76 +/- 6, and 67 +/- 5% (P > 0.05) at rest, 3 miles/h, and 6 miles/h, respectively. Systemic blood pressure and blood flow in the contralateral iliac artery were unaffected by phenylephrine. These results do not demonstrate an attenuation of vasoconstriction to a selective alpha1-agonist during exercise and do not support the concept of sympatholysis.

Rapid vasodilation in response to a brief tetanic muscle contraction.

To test the hypothesis that vasodilation occurs because of the release of a vasoactive substance after a brief muscle contraction and to determine whether acetylcholine spillover from the motor nerve is involved in contraction-induced hyperemia, tetanic muscle contractions were produced by sciatic nerve stimulation in anesthetized dogs (n = 16), instrumented with flow probes on both external iliac arteries. A 1-s stimulation of the sciatic nerve at 1. 5, 3, and 10 times motor threshold increased blood flow above baseline (P < 0.01) for 20, 25, and 30 s, respectively. Blood flow was significantly greater 1 s after the contraction ended for 3 and 10 x motor threshold (P < 0.01) and did not peak until 6-7 s after the contraction. The elevations in blood flow to a 1-s stimulation of the sciatic nerve and a 30-s train of stimulations were abolished by neuromuscular blockade (vecuronium). The delayed peak blood flow response and the prolonged hyperemia suggest that a vasoactive substance is rapidly released from the contracting skeletal muscle and can affect blood flow with removal of the mechanical constraint imposed by the contraction. In addition, acetylcholine spillover from the motor nerve is not responsible for the increase in blood flow in response to muscle contraction.

Exercise attenuates alpha-adrenergic-receptor responsiveness in skeletal muscle vasculature.

Attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during dynamic exercise is controversial. A potential mechanism is a reduction in alpha-adrenergic-receptor responsiveness. The purpose of this study was to examine alpha(1)- and alpha(2)-adrenergic-receptor-mediated vasoconstriction in resting and exercising skeletal muscle using intra-arterial infusions of selective agonists. Thirteen mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective alpha(1)-adrenergic agonist (phenylephrine) or the selective alpha(2)-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of 76 +/- 4, 71 +/- 5, and 31 +/- 2% at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by 81 +/- 5, 49 +/- 4, and 14 +/- 2%, respectively. The response to intra-arterial infusion of clonidine was unaffected by surgical sympathetic denervation. Agonist infusion did not affect either systemic blood pressure, heart rate, or blood flow in the contralateral iliac artery. alpha(1)-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, alpha(2)-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. These results suggest that the mechanism of exercise sympatholysis may involve reductions in postsynaptic alpha-adrenergic-receptor responsiveness.

Reinnervation of pulmonary stretch receptors.

The Breuer-Hering reflex (BHR) reappears 12-14 wk after surgical lung denervation in beagle dogs (J. Appl. Physiol. 54: 1451-1456, 1983). To demonstrate that this is due to reinnervation of pulmonary stretch receptors, we recorded nerve activity from regenerated branches of the left vagus nerve in five beagle dogs. Ten days postdenervation the BHR was absent, whereas by 19 mo it was clearly present. Multifiber pulmonary afferent activity was observed in all five dogs with single-fiber activity observed in three. Sectioning the right vagus nerve did not alter the BHR, but sectioning all the regenerated branches of the left vagus abolished the reflex. In two additional dogs studied 17 mo postsurgery, recordings were made from few fiber nerve bundles of the left cervical vagus. Nerve activity was increased during gentle stroking of the surface of the left upper and lower lobes, indicating receptive fields in both lobes. These data demonstrate that reinnervation of pulmonary stretch receptors does occur and provides evidence that reinnervation of these receptors is responsible for return of the BHR after pulmonary denervation.

Effect of chronic pulmonary denervation on ventilatory responses to exercise.

To assess the role of intrapulmonary receptors on the ventilatory responses to exercise we studied six beagle dogs before and after chronic pulmonary denervation and five dogs before and after sham thoracotomies. Each exercise challenge consisted of 6 min of treadmill exercise with measurements taken during the third minute at 3.2 km/h, 0% grade, and during the third minute at 5.0 km/h, 0% grade. Inspiratory and expiratory airflows were monitored with a low-dead-space latex mask and pneumotachographs coupled to differential pressure transducers. Both pre- and postsurgery, all dogs exhibited a significant arterial hypocapnia and alkalosis during exercise. Denervation of the lungs had no significant effect on minute ventilation at rest or during exercise, although there was a lower frequency and higher tidal volume in the lung-denervated dogs at all measurement periods. Breathing frequency increased significantly during exercise in lung-denervated dogs but to a lesser magnitude than in the control dogs. The changes that occurred in breathing frequency in all animals were due predominantly to the shortening of expiratory time. Inspiratory time did not shorten significantly during exercise following lung denervation. We conclude from these data that intrapulmonary receptors which are deafferented by sectioning the vagi at the hilum are not responsible for setting the level of ventilation during rest or exercise but are involved in determining the pattern of breathing.

Influence of body size on oxygen consumption during bicycling.

Energy in bicycling is primarily expended to overcome air resistance, which is proportional to a cyclist's surface area (SA). Thus we hypothesized that large cyclists should have a lower O2 consumption normalized to body weight (VO2/BW) than small cyclists because of the former's lower SA/BW. We measured the VO2/BW of small (BW = 59.4 +/- 4.1 kg) and large (BW = 84.4 +/- 3.2 kg) cyclists while they bicycled on a flat road at 10, 15, and 20 mph. The large cyclists had a 22% lower VO2/BW than the small cyclists at all speeds. However, the SA/BW ratio of the large cyclists was only 11% lower than that of the small cyclists. We then photographically determined the frontal area (FA) of the cyclists in a racing posture, and found that the large cyclists had a 16% lower FA/BW ratio than the small cyclists. We conclude that large cyclists are at a distinct advantage, in terms of VO2/BW, while bicycling on level roads, and this advantage is principally due to their lower FA/BW ratio.

Effect of dynamic exercise on renal sympathetic nerve activity in conscious rabbits.

Renal sympathetic nerve activity (RSNA) increases abruptly at the onset of treadmill exercise in conscious rabbits. This study investigated whether the rise in RSNA is related to the intensity of the exercise and whether an elevated level of RSNA is maintained during submaximal exercise. RSNA, arterial blood pressure (BP), and heart rate (HR) were recorded in 10 New Zealand White rabbits during two treadmill exercise protocols at 0% grade: 7 m/min for 5 min and 12 m/min for 2 min. Peak levels of RSNA were observed in the first 10 s of exercise at 7 and 12 m/min. Through 2 min of exercise, the rise in RSNA was greater (P < 0.05) at 12 m/min (delta 83 +/- 22%) compared with 7 m/min (delta 49 +/- 8%). At 7 m/min, HR and BP reached steady-state levels during the 2nd min of exercise. RSNA remained elevated at delta 43 +/- 10 to delta 54 +/- 13% over resting levels as exercise continued from the 2nd through the 5th min of exercise (P < 0.05). These data demonstrate that the RSNA response to exercise is intensity related and suggest that RSNA remains elevated and thus may contribute to the control of renal blood flow during submaximal dynamic exercise.

Noninvasive diffusing capacity and cardiac output in exercising dogs.

We have developed a rebreathing procedure to determine diffusing capacity (DLCO) and pulmonary blood flow (Qc) in the awake, exercising dog. A low dead space, leak-free respiratory mask with an incorporated mouthpiece was utilized to achieve mixing between the rebreathing bag and the dog's lung. The rebreathing bag was initially filled with approximately 1.0 liter of gas containing 0.6% C2H2, 0.3% C18O, 9% He, and 35-40% O2. End-tidal gas concentrations were measured with a respiratory mass spectrometer. The disappearance of C2H2 and C18O was measured with respect to He to calculate Qc and DLCO. Values for DLCO in dogs, expressed per kilogram of body weight, were much larger than those reported in humans. However, at a given level of absolute O2 consumption, measurements of absolute DLCO in dogs were comparable to those reported in humans by both rebreathing and steady-state methods at rest and near-maximal exercise. These results suggest that DLCO is more closely matched to the metabolic capacity (i.e., maximal O2 consumption) than to body size between these two species.

Phenyl biguanide does not inhibit locomotion in conscious rabbits.

Stimulation of cardiopulmonary vagal C fibers with phenyl biguanide (PBG) reflexly inhibits locomotion in addition to causing depression of blood pressure (BP), heart rate (HR), and respiration in cats and rats. We investigated whether PBG caused somatomotor inhibition during exercise in the rabbit, a species in which it is known that the hemodynamic and respiratory responses to PBG are mediated by cardiac rather than by pulmonary receptors. In eight New Zealand White rabbits, BP, HR, and hindlimb electromyographic (EMG) responses to 60 and 120 micrograms/kg PBG and saline vehicle were evaluated during two separate 3-min exercise bouts at 10 m/min at 0% grade. During exercise, 60 micrograms/kg PBG decreased BP (-27 +/- 4 mmHg) and HR (-95 +/- 16 beats/min) but did not inhibit locomotion as suggested by the EMG response (+112 +/- 8% of preinfusion EMG). Hemodynamic and EMG responses to 120 micrograms/kg PBG were similar to 60 micrograms/kg PBG. Saline infusion during exercise had no effect on HR, BP, or locomotion (+114 +/- 8% of preinfusion EMG). Locomotion is not inhibited by PBG in rabbits, which suggests that PBG-induced reflex somatomotor inhibition observed in other species is primarily mediated by pulmonary rather than by cardiac receptors.