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Sympatholytic effect of calcitonin gene‐related peptide in rat soleus and gastrocnemius feed arteries
Author(s) -
Brown Megan E.,
Humphries M. Harrison,
Moore Brittni N.,
Jasperse Jeffrey L.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb681
Subject(s) - calcitonin gene related peptide , vasodilation , medicine , endocrinology , vasoconstriction , chemistry , phenylephrine , methoxamine , agonist , anatomy , receptor , blood pressure , neuropeptide
Exercise has been shown to increase sympathetic nerve activity and augment the release of the neurotransmitter norepinephrine at the arterial wall and into the blood. Norepinephrine binds to arterial adrenergic receptors causing vasoconstriction, yet arteries and arterioles constrict less to sympathetic stimulation in contracting skeletal muscle in comparison to resting skeletal muscle. This phenomenon is defined as sympatholysis. Calcitonin gene‐related peptide (CGRP) is a potent vasodilator initially studied in the cerebral circulation but with effects on vascular beds throughout the peripheral circulation. In skeletal muscle, CGRP is released from both sensory and motor neurons. Therefore, we hypothesized that increased levels of CGRP could contribute to sympatholysis. Dose response curves to CGRP (10 −12 M to 10 −6 M) in soleus feed arteries (SFA) and gastrocnemius feed arteries (GFA) isolated from male Sprague‐Dawley rats were used to compare the vasodilation response to CGRP in muscles of different fiber type. SFA (n = 12) and GFA (n = 8) were isolated and cannulated on two glass micropipettes for in vitro videomicroscopy. Both SFA and GFA dilated significantly to CGRP (SFA: 93.6 ± 2.5% and GFA: 87.8 ± 4.5%) and there was no difference between SFA and GFA in the maximal dilation or sensitivity to CGRP. The constriction response to the α‐1 agonist phenylephrine (PE; 10 −9 M to 10 −4 M, 0.5 log increments) was measured under control conditions and in the presence of two levels of CGRP (Low: 0.5 nM and Medium: 50 nM) in SFA (n = 6) and GFA (n = 5). Maximal constriction to PE was reduced by CGRP (Control: 82.2 ± 4.4%, Low: 68.4 ± 4.3%, Medium: 70.4 ± 5.1%). Sensitivity to PE (EC 50 ) was also reduced by CGRP. In GFA, neither maximal dilation nor sensitivity to PE was reduced by CGRP. We conclude that CGRP reduces α‐1 mediated constriction in feed arteries from the predominantly slow‐twitch soleus muscle, but not in feed arteries from the predominantly fast‐twitch gastrocnemius muscle. Support or Funding Information Seaver Research Council of Pepperdine University