ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex in rats

The exercise pressor reflex is due to activation of thin fiber afferents within contracting muscle. These afferents are in part stimulated by ATP activation of purinergic 2X (P2X) receptors during contraction. Which of the P2X receptors contribute to the reflex is unknown; however, P2X2/3 and P2X3 receptor subtypes are good candidates because they are located on thin fiber afferents and are involved in sensory neurotransmission. To determine if P2X2/3 and P2X3 receptors evoke the metabolic component of the exercise pressor reflex, we examined the effect of two P2X2/3 and P2X3 antagonists, A-317491 (10 mg/kg) and RO-3 (10 mg/kg), on the pressor response to injections of α,β-methylene ATP (α,β-MeATP; 50 μg/kg), freely perfused static contraction, contraction of the triceps surae muscles while the circulation was occluded, and postcontraction circulatory occlusion in decerebrate cats. We found that the antagonists reduced the pressor response to α,β-MeATP injection (before Δ 20 ± 3 mmHg; drug Δ 11 ± 3 mmHg; P < 0.05), suggesting the antagonists were effective in blocking P2X2/3 and P2X3 receptors. P2X2/3 and P2X3 receptor blockade reduced the pressor response to freely perfused contraction (before Δ 33 ± 5 mmHg; drug Δ 15 ± 5 mmHg; P < 0.05), contraction with the circulation occluded (before Δ 52 ± 7 mmHg; drug Δ 20 ± 4 mmHg; P < 0.05), and during postcontraction circulatory occlusion (before Δ 15 ± 1 mmHg; drug Δ 5 ± 1 mmHg; P < 0.05). Our findings suggest that P2X2/3 and P2X3 receptors contribute to the metabolic component of the exercise pressor reflex in decerebrate cats.

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ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex in rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00565.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. H78-H89 ◽

Cited By ~ 2

Author(s):

Guillaume P. Ducrocq ◽

Joyce S. Kim ◽

Juan A. Estrada ◽

Marc P. Kaufman

Keyword(s):

Lactic Acid ◽

Ion Channel ◽

Pressor Response ◽

Triceps Surae ◽

Exercise Pressor Reflex ◽

Metabolic Component ◽

Pressor Responses ◽

Static Contraction ◽

Pressor Reflex ◽

Triceps Surae Muscles

The role of the acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex is unknown, despite the fact that ASIC1a is opened by decreases in pH in the physiological range. This fact prompted us to test the hypothesis that ASIC1a plays an important role in evoking the exercise pressor reflex in decerebrated rats with freely perfused hindlimb muscles. To test this hypothesis, we measured the effect of injecting two ASIC1a blockers into the arterial supply of the triceps surae muscles on the reflex pressor responses to four maneuvers, namely 1) static contraction of the triceps surae muscles (i.e., the exercise pressor reflex), 2) calcaneal tendon stretch, 3) intra-arterial injection of lactic acid, and 4) intra-arterial injection of diprotonated phosphate. We found that the 2 ASIC1a blockers, psalmotoxin-1 (200 ng/kg) and mambalgin-1 (6.5 μg/kg), decreased the pressor responses to static contraction as well as the peak pressor responses to injection of lactic acid and diprotonated phosphate. In contrast, neither ASIC1a blocker had any effect on the pressor responses to tendon stretch. Importantly, we found that ASIC1a blockade significantly decreased the pressor response to static contraction after a latency of at least 8 s. Our results support the hypothesis that ASIC1a plays a key role in evoking the metabolic component of the exercise pressor reflex. NEW & NOTEWORTHY The role played by acid-sensing ion channel 1a (ASIC1a) in evoking the exercise pressor reflex remains unknown. In decerebrated rats with freely perfused femoral arteries, blocking ASIC1a with psalmotoxin-1 or mambalgin-1 significantly attenuated the pressor response to static contraction, lactic acid, and diprotonated phosphate injection but had no effect on the pressor response to stretch. We conclude that ASIC1a plays a key role in evoking the exercise pressor reflex by responding to contraction-induced metabolites, such as protons.

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ASIC1a does not play a role in evoking the metabolic component of the exercise pressor reflex in a rat model of peripheral artery disease

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00257.2020 ◽

2020 ◽

Vol 319 (1) ◽

pp. H171-H182

Author(s):

Guillaume P. Ducrocq ◽

Joyce S. Kim ◽

Juan A. Estrada ◽

Marc P. Kaufman

Keyword(s):

Quality Of Life ◽

Peripheral Artery Disease ◽

Rat Model ◽

Peripheral Artery ◽

Exercise Pressor Reflex ◽

Metabolic Component ◽

Pressor Reflex ◽

Artery Disease

The role of ASIC1a in evoking the metabolic component of the exercise pressor reflex in peripheral artery disease is unknown. Using a within-rat experimental design, we found that the contribution of ASIC1a decreased in a rat model of peripheral artery disease. These results have key implications to help finding better treatments and improve morbidity, quality of life, and mortality in patients with peripheral artery disease.

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Exercise Pressor Reflex is Altered in Korean Obese Children

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000401251.60337.81 ◽

2011 ◽

Vol 43 (Suppl 1) ◽

pp. 454

Author(s):

Kwang-IL Kim ◽

Hyun-Min Choi ◽

Joon-Hee Lee ◽

Jong-Mok Chun ◽

Woo-Ram Han ◽

...

Keyword(s):

Obese Children ◽

Exercise Pressor Reflex ◽

Pressor Reflex

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Mechanoreflex Mediates the Exaggerated Exercise Pressor Reflex in Heart Failure

Circulation ◽

10.1161/circulationaha.105.566745 ◽

2005 ◽

Vol 112 (15) ◽

pp. 2293-2300 ◽

Cited By ~ 78

Author(s):

Scott A. Smith ◽

Jere H. Mitchell ◽

R. Haris Naseem ◽

Mary G. Garry

Keyword(s):

Heart Failure ◽

Exercise Pressor Reflex ◽

Pressor Reflex

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Chronic femoral artery ligation exaggerates the pressor and sympathetic nerve responses during dynamic skeletal muscle stretch in decerebrate rats

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00498.2017 ◽

2018 ◽

Vol 314 (2) ◽

pp. H246-H254 ◽

Cited By ~ 6

Author(s):

Evan A. Kempf ◽

Korynne S. Rollins ◽

Tyler D. Hopkins ◽

Alec L. Butenas ◽

Joseph M. Santin ◽

...

Keyword(s):

Blood Pressure ◽

Peripheral Artery Disease ◽

Sympathetic Nerve ◽

Sympathetic Nerve Activity ◽

Peripheral Artery ◽

Nerve Activity ◽

Exercise Pressor Reflex ◽

Pressor Reflex ◽

Artery Disease ◽

Dynamic Stretch

Mechanical and metabolic signals arising during skeletal muscle contraction reflexly increase sympathetic nerve activity and blood pressure (i.e., the exercise pressor reflex). In a rat model of simulated peripheral artery disease in which a femoral artery is chronically (~72 h) ligated, the mechanically sensitive component of the exercise pressor reflex during 1-Hz dynamic contraction is exaggerated compared with that found in normal rats. Whether this is due to an enhanced acute sensitization of mechanoreceptors by metabolites produced during contraction or involves a chronic sensitization of mechanoreceptors is unknown. To investigate this issue, in decerebrate, unanesthetized rats, we tested the hypothesis that the increases in mean arterial blood pressure and renal sympathetic nerve activity during 1-Hz dynamic stretch are larger when evoked from a previously “ligated” hindlimb compared with those evoked from the contralateral “freely perfused” hindlimb. Dynamic stretch provided a mechanical stimulus in the absence of contraction-induced metabolite production that closely replicated the pattern of the mechanical stimulus present during dynamic contraction. We found that the increases in mean arterial blood pressure (freely perfused: 14 ± 1 and ligated: 23 ± 3 mmHg, P = 0.02) and renal sympathetic nerve activity were significantly greater during dynamic stretch of the ligated hindlimb compared with the increases during dynamic stretch of the freely perfused hindlimb. These findings suggest that the exaggerated mechanically sensitive component of the exercise pressor reflex found during dynamic muscle contraction in this rat model of simulated peripheral artery disease involves a chronic sensitizing effect of ligation on muscle mechanoreceptors and cannot be attributed solely to acute contraction-induced metabolite sensitization. NEW & NOTEWORTHY We found that the pressor and sympathetic nerve responses during dynamic stretch were exaggerated in rats with a ligated femoral artery (a model of peripheral artery disease). Our findings provide mechanistic insights into the exaggerated exercise pressor reflex in this model and may have important implications for peripheral artery disease patients.

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