ATP-sensitive potassium channels mediate vasodilatation produced by calcitonin gene-related peptide in human internal mammary but not gastroepiploic arteries.
The purpose of this study was to elucidate the mechanism of action of calcitonin gene-related peptide-induced vasodilatation of human gastroepiploic and internal mammary arteries. Calcitonin gene-related peptide (0.1-100 nmol L-1) elicited relaxations of preconstricted vessels, with a significantly greater effect in the gastroepiploic artery (P < 0.05). This effect was independent of endothelium-derived vasodilating substances. The response of the internal mammary artery but not the gastroepiploic artery to calcitonin gene-related peptide was attenuated by glybenclamide (1.0 mumol L-1) (P < 0.05). In vitro autoradiography indicated that [125I]-calcitonin gene-related peptide bound to the tunica media but not the endothelial cells in both types of artery, with a significantly higher degree of binding in the gastroepiploic artery. It is concluded that calcitonin gene-related peptide acts directly on vascular smooth muscle via specific binding sites to induce vasodilatation. In addition, KATP channels are involved in the action of calcitonin gene-related peptide in the internal mammary artery but not in the gastroepiploic artery.
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Department of Cardiothoracic Surgery, Imperial College of Science Technology & Medicine, Heart Science Centre, Harefield Hospital, Middlesex, UK.
Dashwood
M R
MR
Tadjkarimi
S
S
Chester
A H
AH
Yacoub
M H
MH
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001665:Binding Sites; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology*; D002648:Child; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D009204:Myocardial Revascularization; D015221:Potassium Channels / Q000502:physiology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects*
D015221:Potassium Channels; D018015:Receptors, Calcitonin Gene-Related Peptide; D000255:Adenosine Triphosphate; D015740:Calcitonin Gene-Related Peptide