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Journal of Applied Physiology... Oct 2018It remains unknown whether cutaneous adrenergic nerves functionally contribute to sweat production during exercise. This study examined whether cutaneous adrenergic... (Comparative Study)
Comparative Study
It remains unknown whether cutaneous adrenergic nerves functionally contribute to sweat production during exercise. This study examined whether cutaneous adrenergic nerve blockade attenuates sweating during incremental exercise, specifically in habitually trained individuals. Accordingly, 10 habitually trained and 10 untrained males (V̇o: 56.7 ± 5.4 and 38.9 ± 6.7 ml·kg·min, respectively; P < 0.001) performed incremental semirecumbent cycling (20 W/min) until exhaustion. Sweat rates (ventilated capsule) were measured at two bilateral forearm skin sites on which either 10 mM bretylium tosylate (BT) (an inhibitor of neurotransmitter release from sympathetic adrenergic nerve terminals) or saline (Control) was transdermally administered via iontophoresis. BT treatment delayed sweating onset in both groups (∼0.66 min; P = 0.001) and suppressed the sweat rate relative to the Control treatment at ≥70% relative total exercise time in trained individuals (each 10% increment; all P ≤ 0.009) but not in untrained counterparts ( P = 0.122, interaction between relative time × treatment). Changes in total sweat production at the BT site relative to the Control site were greater in trained individuals than in untrained counterparts (area under the curve, -0.86 ± 0.67 and -0.22 ± 0.39 mg/cm, respectively; P = 0.023). In conclusion, we demonstrated that cutaneous adrenergic nerves do modulate sweating during incremental exercise, which appeared to be more apparent in habitually trained men (e.g., ≥70% maximum workload). Although our results indicated that habitual exercise training may augment neural adrenergic sweat production during incremental exercise, additional studies are required to confirm this possibility. NEW & NOTEWORTHY We demonstrated for the first time that cutaneous adrenergic nerves do modulate sweating during high-intensity exercise in humans (≥70% maximum workload). In addition, neural adrenergic sweating appeared to be greater in habitually trained individuals than in untrained counterparts, although further studies are necessary to confirm such a possibility. Nonetheless, the observations presented herein advance our understanding on human thermoregulation while providing new evidence for the neutral mediation of adrenergic sweating during exercise.
Topics: Adrenergic Fibers; Bretylium Tosylate; Exercise; Humans; Male; Physical Fitness; Sweat Glands; Young Adult
PubMed: 30024338
DOI: 10.1152/japplphysiol.00370.2018 -
British Journal of Pharmacology Oct 19811 Effects of (--)-, (+/-)-, and (+)-propranolol, atenolol, guanethidine, bretylium and tetracaine were studied on relaxation responses of rabbit ileum and contractile... (Comparative Study)
Comparative Study
1 Effects of (--)-, (+/-)-, and (+)-propranolol, atenolol, guanethidine, bretylium and tetracaine were studied on relaxation responses of rabbit ileum and contractile responses of rabbit pulmonary artery and guinea-pig vas deferens to electrical nerve stimulation (2 to 50 Hz). 2 In the ileum, inhibition by tetracaine 3.3 x 10(-6) M occurred at high frequencies of stimulation, while bretylium 1.2 x 10(-4) M and guanethidine 2 x 10(-5) M inhibited responses at all frequencies, the latter producing greater inhibition at low frequencies. 3 (+/-)-Propranolol 10(-5) M produced a tetracaine-type inhibition after 1 h and a bretylium-pattern after 2 h in the ilea and pulmonary arteries and a transition from bretylium- to guanethidine-pattern in the vas deferens, while atenolol 2 x 10(-5) to 10(-4) M produced guanethidine-type inhibition in all preparations. 4 (--)-, (+/-)-, and (+)-Propranolol 3 x 10(-6) to 3.3 x 10(-5) M were equipotent in the vas deferens and ileum. However, inhibition by (--)-propranolol 3.3 x 10(-5) M persisted in the ileum, while that by the (+)-isomer was partially restored by washing. 5 (--)- or (+)-Propranolol 3.3 x 10(-5) M or atenolol 2 x 10(-5) M did not inhibit relaxation of the ileum after the bath temperature was maintained at 4 degrees C for 2 h during drug application. 6 In conclusion, propranolol and atenolol both have gradually developing guanethidine-like adrenergic neurone blocking actions.
Topics: Animals; Atenolol; Bretylium Compounds; Bretylium Tosylate; Guanethidine; Guinea Pigs; Ileum; Male; Propanolamines; Propranolol; Pulmonary Artery; Rabbits; Stereoisomerism; Sympathetic Nervous System; Synaptic Transmission; Tetracaine; Vas Deferens
PubMed: 6274462
DOI: 10.1111/j.1476-5381.1981.tb09980.x -
Journal of Applied Physiology... May 1999To determine the effect and underlying mechanisms of exercise training and the influence of age on the skin blood flow (SkBF) response to exercise in a hot environment,... (Clinical Trial)
Clinical Trial Comparative Study
To determine the effect and underlying mechanisms of exercise training and the influence of age on the skin blood flow (SkBF) response to exercise in a hot environment, 22 young (Y; 18-30 yr) and 21 older (O; 61-78 yr) men were assigned to 16 wk of aerobic (A; YA, n = 8; OA, n = 11), resistance (R; YR, n = 7; OR, n = 3), or no training (C; YC, n = 7; OC, n = 7). Before and after treatment, subjects exercised at 60% of maximum oxygen consumption (VO2 max) on a cycle ergometer for 60 min at 36 degrees C. Cutaneous vascular conductance, defined as SkBF divided by mean arterial pressure, was monitored at control (vasoconstriction intact) and bretylium-treated (vasoconstriction blocked) sites on the forearm using laser-Doppler flowmetry. Forearm vascular conductance was calculated as forearm blood flow (venous occlusion plethysmography) divided by mean arterial pressure. Esophageal and skin temperatures were recorded. Only aerobic training (functionally defined a priori as a 5% or greater increase in VO2 max) produced a decrease in the mean body temperature threshold for increasing forearm vascular conductance (36.89 +/- 0.08 to 36.63 +/- 0.08 degrees C, P < 0.003) and cutaneous vascular conductance (36.91 +/- 0.08 to 36.65 +/- 0.08 degrees C, P < 0.004). Similar thresholds between control and bretylium-treated sites indicated that the decrease was mediated through the active vasodilator system. This shift was more pronounced in the older men who presented greater training-induced increases in VO2 max than did the young men (22 and 9%, respectively). In summary, older men improved their SkBF response to exercise-heat stress through the effect of aerobic training on the cutaneous vasodilator system.
Topics: Adolescent; Adult; Aged; Aging; Body Composition; Body Temperature; Bretylium Tosylate; Exercise; Heat Stress Disorders; Humans; Male; Middle Aged; Oxygen Consumption; Physical Fitness; Regional Blood Flow; Skin; Sympatholytics; Vasoconstriction; Vasodilation
PubMed: 10233135
DOI: 10.1152/jappl.1999.86.5.1676 -
Journal of Applied Physiology... Mar 2005The role of skin temperature in reflex control of the active cutaneous vasodilator system was examined in six subjects during mild graded heat stress imposed by... (Clinical Trial)
Clinical Trial
The role of skin temperature in reflex control of the active cutaneous vasodilator system was examined in six subjects during mild graded heat stress imposed by perfusing water at 34, 36, 38, and 40 degrees C through a tube-lined garment. Skin sympathetic nerve activity (SSNA) was recorded from the peroneal nerve with microneurography. While monitoring esophageal, mean skin, and local skin temperatures, we recorded skin blood flow at bretylium-treated and untreated skin sites by using laser-Doppler velocimetry and local sweat rate by using capacitance hygrometry on the dorsal foot. Cutaneous vascular conductance (CVC) was calculated by dividing skin blood flow by mean arterial pressure. Mild heat stress increased mean skin temperature by 0.2 or 0.3 degrees C every stage, but esophageal and local skin temperature did not change during the first three stages. CVC at the bretylium tosylate-treated site (CVC(BT)) and sweat expulsion number increased at 38 and 40 degrees C compared with 34 degrees C (P < 0.05); however, CVC at the untreated site did not change. SSNA increased at 40 degrees C (P < 0.05, different from 34 degrees C). However, SSNA burst amplitude increased (P < 0.05), whereas SSNA burst duration decreased (P < 0.05), at the same time as we observed the increase in CVC(BT) and sweat expulsion number. These data support the hypothesis that the active vasodilator system is activated by changes in mean skin temperature, even at normal core temperature, and illustrate the intricate competition between active vasodilator and the vasoconstrictor system for control of skin blood flow during mild heat stress.
Topics: Adult; Body Temperature; Body Temperature Regulation; Bretylium Compounds; Female; Heat Stress Disorders; Humans; Male; Reflex; Rest; Skin; Sympathetic Nervous System; Vasodilation
PubMed: 15489258
DOI: 10.1152/japplphysiol.00235.2004 -
American Journal of Physiology.... Nov 2004To test the hypothesis that cutaneous vasoconstrictor responsiveness to exogenous norepinephrine is reduced in older compared with young subjects, dose-response... (Clinical Trial)
Clinical Trial Comparative Study
To test the hypothesis that cutaneous vasoconstrictor responsiveness to exogenous norepinephrine is reduced in older compared with young subjects, dose-response relations between norepinephrine and skin blood flow were established. Seven doses of norepinephrine (1.10(-8) to 10(-2) log M) were perfused (2 microl/min) intradermally (4 min/dose) using cutaneous microdialysis (2 probes/subject). To account for possible differences in endogenous norepinephrine between groups, one microdialysis probe was perfused with bretylium tosylate to locally block noradrenergic vesicle release before establishing the norepinephrine dose-response relations. Skin blood flow was indexed via laser-Doppler flowmetry directly over both microdialysis probe sites and is expressed as cutaneous vascular conductance (laser-Doppler flux/mean arterial blood pressure). Local skin temperature was maintained at 34 degrees C at both sites throughout the protocol. Dose-response relation between norepinephrine and cutaneous vascular conductance was similar between control and bretylium-pretreated sites in young subjects (EC50 = -5.18 +/- 0.27 and -5.03 +/- 0.27 log M, respectively). In contrast, the dose-response relation was significantly shifted to the right (i.e., a higher dose of norepinephrine was needed to produce the same vasoconstrictor response) in the bretylium-pretreated site in older subjects (EC50 = -5.46 +/- 0.23 and -4.53 +/- 0.23 log M, respectively). Significant increases in EC50 were observed in older compared with young subjects at the bretylium-pretreated but not the control sites. These data indicate that cutaneous vasoconstrictor responsiveness is decreased in older subjects when endogenous release of norepinephrine is antagonized. Furthermore, these findings suggest that differences in presynaptic norepinephrine release between older and younger subjects are profound enough to affect dose-response relations between norepinephrine and cutaneous vascular conductance.
Topics: Adolescent; Adrenergic Agents; Adult; Aged; Aging; Bretylium Tosylate; Cold Temperature; Dose-Response Relationship, Drug; Female; Humans; Male; Microdialysis; Middle Aged; Norepinephrine; Regional Blood Flow; Skin; Stress, Physiological; Vasoconstrictor Agents
PubMed: 15475505
DOI: 10.1152/ajpregu.00467.2004 -
Thorax Jul 1971Five selected cases of successful prolonged resuscitation (up to 16 hours) after open heart surgery are presented. Four had undergone prosthetic valve insertion, two...
Five selected cases of successful prolonged resuscitation (up to 16 hours) after open heart surgery are presented. Four had undergone prosthetic valve insertion, two being double replacements. External cardiac massage did not produce any demonstrable damage to the heart or the implanted valve prostheses, the competent prostheses probably assuring the haemodynamic effectiveness of the massage. Intermittent positive pressure breathing via an endotracheal tube providing 100% oxygen was begun immediately in all cases. The continuous monitoring of blood pressure through an intra-arterial cannula during resuscitation was of great value. It indicated the minimum amount of force that had to be applied to obtain satisfactory perfusion and enabled frequent arterial blood sampling for pH and blood gas analyses. Thus acidosis could rapidly and effectively be corrected. Comment is made upon the use of bretylium tosylate and chlorpromazine during resuscitation. The value of the continuous presence of a physician at the bedside of patients after open heart surgery and an aggressive, stubborn approach to cardiopulmonary resuscitation as long as vital signs are present is stressed.
Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Blood Gas Analysis; Blood Pressure; Bradycardia; Bretylium Compounds; Cardiac Surgical Procedures; Chlorpromazine; Electrocardiography; Female; Heart Arrest; Heart Massage; Heart Valve Prosthesis; Humans; Hydrogen-Ion Concentration; Middle Aged; Positive-Pressure Respiration; Resuscitation; Ventricular Fibrillation
PubMed: 4935672
DOI: 10.1136/thx.26.4.449 -
Journal of Applied Physiology... Nov 1996We sought to identify whether reductions in cutaneous active vasodilation during simulated orthostasis could be assigned solely to cardiopulmonary or to carotid... (Clinical Trial)
Clinical Trial
We sought to identify whether reductions in cutaneous active vasodilation during simulated orthostasis could be assigned solely to cardiopulmonary or to carotid baroreflexes by unloading cardiopulmonary baroreceptors with low levels of lower body negative pressure (LBNP) or unloading carotid baroreceptors with external pressure applied over the carotid sinus area [carotid pressure (CP)]. Skin blood flow was measured at a site at which adrenergic function was blocked via bretylium tosylate iontophoresis and at an unblocked site. During LBNP of -5 and -10 mmHg in hyperthermia, neither heart rate (HR) nor cutaneous vascular conductance (CVC) at either site changed (P > 0.05 for both), whereas forearm vascular conductance (FVC) was reduced (-5 mmHg: from 21.6 +/- 4.8 to 19.8 +/- 4.1 FVC units, P = 0.05; -10 mmHg: from 22.3 +/- 4.0 to 19.3 +/- 3.7 FVC units, P = 0.002). LBNP of -30 mmHg in hyperthermia reduced CVC at both sites (untreated: from 51.9 +/- 5.7 to 43.2 +/- 5.1% maximum, P = 0.02; bretylium tosylate: from 60.9 +/- 5.4 to 53.2 +/- 4.4% maximum, P = 0.02), reduced FVC (from 23.2 +/- 3.6 to 18.1 +/- 3.3 FVC units; P = 0.002), and increased HR (from 83 +/- 4 to 101 +/- 3 beats/min; P = 0.003). Pulsatile CP (45 mmHg) did not affect FVC or CVC during normothermia or hyperthermia (P > 0.05). However, HR and mean arterial pressure were elevated during CP in both thermal conditions (both P < 0.05). These results suggest that neither selective low levels of cardiopulmonary baroreceptor unloading nor selective carotid baroreceptor unloading can account for the inhibition of cutaneous active vasodilator activity seen with simulated orthostasis.
Topics: Adult; Baroreflex; Blood Pressure; Cold Temperature; Female; Heart Rate; Humans; Lower Body Negative Pressure; Male; Pressoreceptors; Regional Blood Flow; Skin; Skin Temperature; Stress, Physiological; Vasodilation
PubMed: 8941544
DOI: 10.1152/jappl.1996.81.5.2192 -
The Journal of Physiology Jul 2004Cutaneous vasoconstriction (VC) in response to cooling is attenuated in older humans; however, mechanisms underlying this functional decline remain unclear. The present... (Comparative Study)
Comparative Study
Cutaneous vasoconstriction (VC) in response to cooling is attenuated in older humans; however, mechanisms underlying this functional decline remain unclear. The present study tested the hypothesis that the contributions of noradrenaline (NA) and sympathetic cotransmitters to reflex-mediated cutaneous VC are altered with age. In 11 young (18-26 years) and 11 older (61-77 years) men and women, forearm skin blood flow was monitored at three sites using laser Doppler flowmetry (LDF) while mean skin temperature was lowered from 34 to 30.5 degrees C using a water-perfused suit. Cutaneous vascular conductance (CVC; LDF/mean arterial pressure) was expressed as percentage change from baseline (% DeltaCVC(base)). Solutions of yohimbine + propranolol (Y + P), bretylium tosylate (BT), and lactated Ringer solution were infused via intradermal microdialysis at each LDF site to antagonize alpha- and beta-adrenoceptors, block sympathetic release of NA and cotransmitters, and act as control, respectively. During cooling, VC was attenuated at the control site in older subjects compared to young subjects (-16 +/- 3 versus-34 +/- 4% DeltaCVC(base), P < 0.001). Y + P attenuated VC in young subjects (-13 +/- 8% DeltaCVC(base), P < 0.001 versus control) and abolished VC in older subjects (0 +/- 3% DeltaCVC(base), P > 0.9 versus baseline). BT completely blocked VC in both age groups. Cutaneous VC in young subjects is mediated by both NA and sympathetic cotransmitter(s); however, reflex VC in aged skin is attenuated compared to young and appears to be mediated solely by NA.
Topics: Adolescent; Adult; Aged; Aging; Female; Humans; Male; Middle Aged; Norepinephrine; Reflex; Skin; Sympathetic Nervous System; Vasoconstriction
PubMed: 15181162
DOI: 10.1113/jphysiol.2004.065714 -
British Heart Journal May 1970The prophylactic value of parenterally administered bretylium tosylate against the onset of dysrhythmias after acute myocardial infarction has been assessed by a... (Clinical Trial)
Clinical Trial
The prophylactic value of parenterally administered bretylium tosylate against the onset of dysrhythmias after acute myocardial infarction has been assessed by a controlled trial in 101 male patients. Bretylium significantly reduced the incidence of supraventricular dysrhythmias but was without significant effect on the incidence of ventricular dysrhythmias. The only serious side-effect of the drug was hypotension which occurred in one-third of the patients. It is concluded that prophylactic treatment of patients suffering from uncomplicated myocardial infarction with parenteral bretylium tosylate probably does not confer sufficient clinical benefit to warrant its recommendation for preventative use in this disease.
Topics: Acute Disease; Adult; Aged; Arrhythmias, Cardiac; Bretylium Compounds; Clinical Trials as Topic; Humans; Hypotension; Male; Middle Aged; Myocardial Infarction
PubMed: 4911756
DOI: 10.1136/hrt.32.3.326 -
Experimental Physiology Nov 2011We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate...
We investigated the roles of sensory and noradrenergic sympathetic nerves on the cutaneous vasodilator response to a localized noxious heating stimulus. In two separate studies, four forearm skin sites were instrumented with microdialysis fibres, local heaters and laser-Doppler probes. Skin sites were locally heated from 33 to 42 °C or rapidly to 44 °C (noxious). In the first study, we tested sensory nerve involvement using EMLA cream. Treatments were as follows: (1) control 42 °C; (2) EMLA 42 °C; (3) control 44°C; and (4) EMLA 44 °C. At the EMLA-treated sites, the axon reflex was reduced compared with the control sites during heating to 42 °C (P < 0.05). There were no differences during the plateau phase (P > 0.05). At both the sites heated to 44 °C, the initial peak and nadir became indistinguishable, and the EMLA-treated sites were lower compared with the control sites during the plateau phase (P < 0.05). In the second study, we tested the involvement of noradrenergic sympathetic nerves in response to the noxious heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42 °C; (2) BT 42 °C; (3) control 44 °C; and (4) BT 44 °C. Treatment with BT at the 42 °C sites resulted in a marked reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44 °C sites, there was no apparent initial peak or nadir, but the plateau phase was reduced at the BT-treated sites (P < 0.05). These data suggest that both sympathetic nerves and sensory nerves are involved during the vasodilator response to a noxious heat stimulus.
Topics: Adult; Anesthetics, Local; Bretylium Tosylate; Female; Hot Temperature; Humans; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Prilocaine; Regional Blood Flow; Skin; Skin Temperature; Sympathetic Nervous System; Vasodilation; Vasodilator Agents
PubMed: 21890519
DOI: 10.1113/expphysiol.2011.059907