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Title: Calcitonin gene-related peptide inhibits angiotensin II-mediated vasoconstriction in human radial arteries: role of the Kir channel.
Austin Authors: Zulli, Anthony;Ye, Bei;Wookey, Peter J ;Buxton, Brian F ;Hare, David L 
Affiliation: Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
Issue Date: 19-Jun-2008
Publication information: The Journal of Thoracic and Cardiovascular Surgery 2008; 136(2): 370-5
Abstract: The radial artery is increasingly used for coronary artery bypass grafts, but its potential for spasm increases postoperative risk. Alpha-calcitonin gene-related peptide is a potent antihypertensive peptide. Thus, we set out to determine whether calcitonin gene-related peptide can impair angiotensin II-mediated vasoconstriction in human radial arteries and, if so, to determine its mechanism of action.Radial arteries were placed in organ bath chambers and preincubated with 10(-9) to 10(-7) mol/L alpha-calcitonin gene-related peptide for 20 minutes before initiating an angiotensin II dose response curve (10(-10)-10(-6) mol/L).Calcitonin gene-related peptide, 10(-7), 10(-8), 3 x 10(-9), and 10(-9) mol/L, reduced angiotensin II-mediated vasoconstriction to 30.5% +/- 7.2% (P < .001), 32.2% +/- 11.7% (P < .001), 62.6% +/- 8.4% (P < .001), and 77.6% +/- 6.7% (P < .01), respectively, compared with control (normalized to 100%). Calcitonin gene-related peptide also significantly decreased basal vascular tension in human radial arteries (P < .05 in all cases). N-nitro-L-arginine methyl ester, 4-aminopyridine, charybdotoxin, and apamin had no effect on calcitonin gene-related peptide relaxation, but Ba(2+) impaired the effects of alpha-calcitonin gene-related peptide.Alpha-calcitonin gene-related peptide dose dependently impaired angiotensin II-mediated vasoconstriction in human radial arteries, independent of nitric oxide and all potassium channels except the barium-sensitive Kir channel. Thus, calcitonin gene-related peptide is an endogenous inhibitor of angiotensin II-mediated vasoconstriction in the human radial artery.
Gov't Doc #: 18692643
DOI: 10.1016/j.jtcvs.2007.12.064
ORCID: 0000-0001-9554-6556
Journal: The Journal of thoracic and cardiovascular surgery
PubMed URL: 18692643
Type: Journal Article
Subjects: 4-Aminopyridine.pharmacology
Angiotensin II.pharmacology
Calcitonin Gene-Related Peptide.pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors.pharmacology
In Vitro Techniques
Middle Aged
NG-Nitroarginine Methyl Ester.pharmacology
Nitric Oxide.antagonists & inhibitors.metabolism
Potassium Channel Blockers.pharmacology
Potassium Channels.metabolism
Radial Artery
Vasoconstriction.drug effects
Vasoconstrictor Agents.pharmacology
Vasodilator Agents.pharmacology
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