Calcitonin gene-related peptide inhibits angiotensin II-mediated vasoconstriction in human radial arteries: role of the Kir channel.
OBJECTIVE
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Zulli
Anthony
A
Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. azulli@unimelb.edu.au
Ye
Bei
B
Wookey
Peter J
PJ
Buxton
Brian F
BF
Hare
David L
DL
D015761:4-Aminopyridine / Q000494:pharmacology; D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D001030:Apamin / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D018999:Charybdotoxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D017534:Radial Artery; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D018999:Charybdotoxin; D001030:Apamin; D001464:Barium; D009569:Nitric Oxide; D015761:4-Aminopyridine; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester