Pharmacological characterisation of endothelium-dependent relaxation in human radial artery: comparison with internal thoracic artery.
OBJECTIVE
The aim of this study was to investigate the contribution of nitric oxide/prostanoid-independent pathways to endothelium-dependent vasorelaxation in human conduit arteries.


METHODS
Rings of internal thoracic artery (ITA) and radial artery (RA) taken from patients undergoing coronary artery bypass graft surgery were suspended in 10-ml organ baths and relaxation to carbachol and bradykinin studied in the presence and absence of nitric oxide synthase (NOS) inhibitors and potassium channel blockers.


RESULTS
No significant relaxation to carbachol or bradykinin was observed in ITA after NOS inhibition. In contrast, in RA less than 40% attenuation of relaxation to carbachol or bradykinin was achieved with any of the NOS inhibitors. In the presence of 20 mM K+ relaxation to carbachol and bradykinin was inhibited by 28 +/- 9% and 42 +/- 9% while in the presence of L-NAME 200 microM + 20 mM K+ relaxation was inhibited by 66 +/- 6% and 70 +/- 4% respectively in this artery. Tetraethylammonium, glibenclamide, apamin and iberiotoxin had little effect on relaxation to carbachol but charybdotoxin alone and charybdotoxin plus apamin attenuated relaxation to carbachol by 23 +/- 4% and 49 +/- 9% in RA. In the presence of L-NAME 200 microM attenuation of these relaxations were increased to 60 +/- 4% and 78 +/- 4%.


CONCLUSIONS
In ITA relaxations to carbachol and bradykinin were mediated via nitric oxide. In contrast in RA, a conduit vessel of similar diameter, both nitric oxide-dependent and independent pathways appeared to contribute to vascular relaxation. This nitric oxide-independent relaxation involved opening of Ca2+ activated potassium channel(s). The existence of alternative pathways mediating endothelium-independent relaxation could be important under pathological conditions and may contribute to the long term survival of radial artery grafts.
Hamilton
C A
CA
Department of Medicine, Western Infirmary, Glasgow, UK.
Williams
R
R
Pathi
V
V
Berg
G
G
McArthur
K
K
McPhaden
A R
AR
Reid
J L
JL
Dominiczak
A F
AF
D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D001026:Coronary Artery Bypass; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D017534:Radial Artery / Q000187:drug effects*; D013895:Thoracic Arteries / Q000187:drug effects; D019737:Transplants; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010656:Phenylephrine; D008825:Miconazole; D002217:Carbachol; D019001:Nitric Oxide Synthase; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester