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The mechano-gated channel inhibitor GsMTx4 reduces the exercise pressor reflex in rats with ligated femoral arteries.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2016 May 01; Vol. 310 (9), pp. H1233-41. Date of Electronic Publication: 2016 Feb 26. - Publication Year :
- 2016
-
Abstract
- Mechanical and metabolic stimuli arising from contracting muscles evoke the exercise pressor reflex. This reflex is greater in a rat model of simulated peripheral arterial disease in which a femoral artery is chronically ligated than it is in rats with freely perfused femoral arteries. The role played by the mechanically sensitive component of the exaggerated exercise pressor reflex in ligated rats is unknown. We tested the hypothesis that the mechano-gated channel inhibitor GsMTx4, a relatively selective inhibitor of mechano-gated Piezo channels, reduces the exercise pressor reflex in decerebrate rats with ligated femoral arteries. Injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced the pressor response to Achilles tendon stretch (a purely mechanical stimulus) but had no effect on the pressor responses to intra-arterial injection of α,β-methylene ATP or lactic acid (purely metabolic stimuli). Moreover, injection of 10 μg of GsMTx4 into the arterial supply of the hindlimb reduced both the integrated pressor area (control 535 ± 21, GsMTx4 218 ± 24 mmHg·s; P < 0.01), peak pressor (control 29 ± 2, GsMTx4 14 ± 3 mmHg; P < 0.01), and renal sympathetic nerve responses to electrically induced intermittent hindlimb muscle contraction (a mixed mechanical and metabolic stimulus). The reduction of the integrated pressor area during contraction caused by GsMTx4 was greater in rats with ligated femoral arteries than it was in rats with freely perfused femoral arteries. We conclude that the mechanically sensitive component of the reflex contributes to the exaggerated exercise pressor reflex during intermittent hindlimb muscle contractions in rats with ligated femoral arteries.<br /> (Copyright © 2016 the American Physiological Society.)
- Subjects :
- Achilles Tendon innervation
Animals
Chemoreceptor Cells metabolism
Decerebrate State
Disease Models, Animal
Electric Stimulation
Hindlimb
Injections, Intra-Arterial
Intercellular Signaling Peptides and Proteins
Ion Channels metabolism
Ligation
Male
Membrane Transport Modulators administration & dosage
Peptides administration & dosage
Rats, Sprague-Dawley
Spider Venoms administration & dosage
Sympathetic Nervous System drug effects
Sympathetic Nervous System metabolism
Sympathetic Nervous System physiopathology
Time Factors
Femoral Artery surgery
Ion Channels antagonists & inhibitors
Mechanotransduction, Cellular drug effects
Membrane Transport Modulators pharmacology
Muscle Contraction
Muscle, Skeletal innervation
Muscle, Skeletal metabolism
Peptides pharmacology
Peripheral Arterial Disease physiopathology
Reflex, Stretch drug effects
Spider Venoms pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1539
- Volume :
- 310
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 26921442
- Full Text :
- https://doi.org/10.1152/ajpheart.00974.2015