| 18692643 |
Zulli A, Ye B, Wookey PJ, Buxton BF, Hare DL: Calcitonin gene-related peptide inhibits angiotensin II-mediated vasoconstriction in human radial arteries: role of the Kir channel. J Thorac Cardiovasc Surg. 2008 Aug;136(2):370-5. Epub 2008 Jun 19.
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. |
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