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presentation of published articled reviewed by Journal of Applied Physiology

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THE ROLE OF ADRENERGIC STIMULATION ON SWEAT

PRODUCTION DURING EXERCISEMichael J. BuonoGabriela Gonzalez

Shaun GuestArabella HareTravis NumanBrian TaborAilish White

Department of Biology and the School of Exercise and Nutritional Sciences

San Diego, CA 92182-7251

INTRODUCTION• Human eccrine sweat gland:

– cholinergic and adrenergic innervation. (19)

INTRODUCTION

Cholinergic Stimulation

β -Adrenergic Stimulation

INTRODUCTION

• Numerous studies: cholinergic stimulation

sweat production during exercise.

(3, 4, 8, 10, 13, 15)

• Other research: β-adrenergic stimulation plays a

less significant role. (8, 10, 13)

INTRODUCTION• Sato and Sato (13):

– eccrine sweat glands with adrenergic receptors

capable of sweating when stimulated with agonists. • e.g. epinephrine, isoproterenol

– in vitro: maximal sweat rate by adrenergic

stimulation 50% of that attained via

cholinergic stimulation.

INTRODUCTION• Several studies: role of adrenergic

stimulation is to potentiate the cholinergic

sweat response (9, 10, 17).

• Ohara et al.– β-adrenergic agonists potentiated neuroglandular transmission of sub- threshold cholinergic responses in humans during thermal sweating.

INTRODUCTION

Purpose of Study:

• To investigate the role of β-adrenergic

stimulation on sweat production during exercise.

• How: atropine block cholinergic

component of thermal sweating.

• isolate any potential adrenergic

response during exercise.

METHODS• Subjects:

– 7 healthy volunteers – Two males– Five females – Signed informed consent prior to testing.

• Means SDs: – age: 25 2 yr– height: 171.8 15.8 cm– weight: 67.2 9.4 kg

• Female subjects:• Urine pregnancy test prior to testing. • All negative.

METHODS• Atropine (1% solution) was

administered to a 5 cm2 area of the flexor surface of one forearm via iontophoresis (1.5 mA) for 5 minutes.

• The opposing arm underwent iontophoresis with a saline solution.– The arm that received the atropine treatment was randomly selected.

METHODS

• Subject then exercised on a motor driven treadmill at 75% of their age-predicted maximal heart rate for five minutes (147 6 bpm).– Heart rate was measured

during exercise using a Polar heart rate monitor.

METHODS• After 5 minute warm-up

period, a Macroduct (Wescor, Logan , UT) was placed on each forearm in order to collect sweat from both of the iontophoresis sites.

• Macroducts were applied after the warm-up period to allow the subjects to begin sweating prior to the initiation of collection

METHODS• Immediately following cessation of exercise skin

temperature of the forearms was measured using an IR technique.

METHODS• The sweat collected in each Macroduct was

determined using a volumetric technique and forearm sweat rate was expressed in mg/cm2/min.

METHODS• The number of active sweat

glands was measured by applying iodine impregnated paper to each site.– Active sweat glands were

counted by the same investigator throughout the study and expressed in glands/cm2.

METHODS

• Pilocarpine was then administered via iontophoresis on the forearm that had Atropine.

• Active sweat glands were measured again with the iodine impregnated paper.

• The mean (± SD) sweat rate in the control arm during exercise was 0.76 ± 0.26 mg/cm2/min.

• Immediately following exercise it was determined that the control arm had an average of 203 ± 51 glands/cm2.

RESULTS

RESULTS

• There was no measurable sweat production in the arm that was pre-treated with atropine during exercise.

• Immediately following exercise, no active sweat glands were detected in the forearm site that was treated with atropine.

• No active sweat glands were detected following pilocarpine iontophoresis.

DISCUSSION• Human sweat glands have dual cholinergic

and adrenergic innervation. (12,13,14,19)• Adrenergic agonists have been shown to induce

sweat via a variety of methods, in vivo (1,3,4,8)

and in vitro (13).

Issues with Previous Studies:• Difficulty maintaining the exact in vivo

concentration of various agonists. (12)

• Effects of injected drugs on local

blood circulation.

• Incomplete blocking of

cholinergic innervation.

DISCUSSION

Our findings:• After full cholinergic blockade, ß-adrenergic innervation

is insufficient to elicit a sudorific response. • Support the previous research from:

– Sonneshien et al. • Combined subthreshold injections of agonists caused

sweating. (17)

– Ohara et al. • ß-adrenergic agonists reduced latency of subthreshold

cholinergic responses when exposed to heat. (9)

DISCUSSION

Our findings (continued):• Sato and Sato.

– Isoproteronol potentiated in vivo, submaximal, cholinergic response from methacholine. (13)

• Robertshaw et al. – Reported that facilitated

cholinergic sweating by epinephrine is similar to its facilitation of cholinergic transmission at the neuromuscular junction. (10)

DISCUSSION

Alternate Explanations:• Cholinergic innervation potentiates ß-adrenergic response.

• Sato and Sato.– Reported cholinergic agonist methacholine significantly augmented the isoproterenal-induced cAMP level in the secretory coil of the simian sweat gland. (14)

– Since ß-adrenergic agonists use the cAMP signaling pathway to evoke sweating such data would suggest that cholinergic agonists potentiate adrenergic stimulation. (14)

DISCUSSION

• Atropine does not effect β -adrenergic sweating.

• Several studies have shown that the use of atropine does not effect β -adrenergic sweating. (8,13,17)

DISCUSSION

• The results of the current study suggest that β-adrenergic stimulation alone is not sufficient to elicit thermal sweating in exercising humans.

• Such data supports previous studies that have suggested that the role of β-adrenergic stimulation is to potentiate cholinergic sweating.

SUMMARY

REFERENCES1. Allen, J, Roddie, I. The role of circulating catelcholamines in sweat production in man. Journal of Physiology 227(3): 801-814, 1972.

2. Buono, M, Jechort, A, Marques, R, Smith, C, Welch, J. Comparison of infrared versus contact thermometry for measuring skin temperature during exercise in the heat. Physiological Measurements 28(8): 855-859, 2007.

3. Foster, K, Weiner, J. Effects of cholinergic and adrenergic blocking agents on the activity of the eccrine sweat glands. Journal of Physiology 210(4): 883-895, 1970.

4. Hurley, HJ, Witkowski, JA. Mechanism of epinephrine-induced eccrine sweating in human skin. Journal of Applied Physiology 16(4): 652-654, 1961.

5. Kolka, MA, Stephonson, LA, Allan, AE, Rock, PB. Atropine-induced cutaneous vasodialation decreases esophageal temperature during exercise. American Journal of Physiology. 257(26): R1089-R1095, 1989.

6. Leuenberger, U, Sinoway, L, Gubin, S, Gual, L, Davis, D, Zelis, R. Effects of exercise intensity and duration on norepinephrine spillover and clearance in humans. Journal of Applied Physiology 75(2): 668-674, 1993.

7. Mack, G, Shannon, L, Nadel, E. Influence of ß-adrenergic blockade on the control of sweating in humans. Journal Applied Physiology 61(5): 1701-1705, 1981.

8. Morgan, C, Friedman, P, Church, M, Clough, G. Cutaneous microdialysis as a novel means of continuously stimulating eccrine sweat glands in vivo. Journal of Investigative Dermatology 126(6): 1220-1225, 2006.

9. Ohara, K, Morita, Y, Okuda, N. Significance of adrenergic transmission in thermal sweating in man. Journal of Thermal Biology 9(1/2): 127-132, 1984.

10. Robertshaw, D, Taylor, C, Mazzia, L. Sweating in primates: secretion by adrenal medulla during exercise. American Journal of Physiology 224(3): 678-681, 1973.

11. Sato, K, Dobson, R. Regional and individual variations in the function of the human eccrine sweat gland. The Journal of Investigative Dermatology 54(6): 443-449, 1970.

12. Sato, K. The physiology, pharmacology and biochemistry of the eccrine sweat gland. Reviews of Physiology, Biochemistry, and Pharmacology 79: 52-131, 1977.

13. Sato, K, Sato, F. Pharmacologic responsiveness of isolated single eccrine sweat glands. American Journal of Physiology 240(1): R44-R51, 1981.

14. Sato, K, Sato, F. Cholinergic potentiation of isoproterenol-induced cAMP level in sweat glands. American Journal of Physiology 245(3): C189-C195, 1983.

15. Shamsuddin, AK, Reddy, MM, Quinton, PM. Iontophoretic ß-adrenergic stimulation of human sweat glands: possible assay for cystic fibrosis transmembrane conductance regulator activity in vivo. Experimental Physiology 93(8): 969-981, 2008.

16. Simpson, K, Green, J, Ellis, F. Effect of glycopyrrolate and atropine on thermoregulation after exercise. British Journal of Clinical Pharmacology 22(5): 579-586, 1986.

17. Sonnenschein, RR, Korbin, HD, Janowitz, HD, Grossman, MI. Stimulation and inhibition of human sweat glands by intradermal sympathomimetic agents. Journal of Applied Physiology 3(10): 573-581, 1951.

18. Terada, E. Effect of adrenaline on human sweating. Journal of the Physiological Society of Japan 28: 176 -183, 1966.

19. Uno, H. Sympathetic innervation of the sweat glands and pilorector muscles of macaques and human beings. Journal of Investigative Dermatology 69: 12-30, 1977.

REFERENCES

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