Sympatholytic effect of calcitonin gene-related peptide in rat soleus and gastrocnemius feed arteries
Presentation Type
Poster
Keywords
Blood flow, exercise, CGRP, sympatholysis
Department
Sports Medicine
Major
Sports Medicine
Abstract
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 (EC50) 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.
Faculty Mentor
Dr. Jeff Jasperse
Location
Waves Cafeteria
Start Date
1-4-2016 2:00 PM
End Date
1-4-2016 3:00 PM
Sympatholytic effect of calcitonin gene-related peptide in rat soleus and gastrocnemius feed arteries
Waves Cafeteria
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 (EC50) 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.