Acta Pharmacologica Sinica 2008 December; 29 (12): 1419-1424; doi: 10.1111/j.1745-7254.2008.00905.x

Acta Pharmacologica Sinica 2008 December; 29 (12): 1419-1424; doi: 10.1111/j.1745-7254.2008.00905.x

Original Article

Endothelium-derived hyperpolarizing factor mediated relaxations in pig coronary arteries do not involve Gi/o proteins^1,2

Kwok Fu Jacobus NG^3,4,5, Susan Wai Sum LEUNG⁴, Ricky Ying Keung MAN⁴, Paul M VANHOUTTE⁴

Departments of ³Anaesthesiology and ⁴Pharmacology, The University of Hong Kong, Hong Kong, China

Aim: Endothelium-dependent relaxations to certain neurohumoral substances are mediated by pertussis toxin-sensitive Gi/o protein. Our experiments were designed to determine the role, if any, of pertussis toxin-sensitive G-proteins in relaxations attributed to endothelium-derived hyperpolarizing factor (EDHF).

Methods: Pig coronary arterial rings with endothelia were suspended in organ chambers filled with Krebs-Ringer bicarbonate solution maintained at 37 ^oC and continuously aerated with 95%O₂ and 5% CO₂. Isometric tension was measured during contractions to prostaglandin F_2αin the presence of indomethacin and N^ω-nitro-L-arginine methyl ester (L-NAME).

Results: Thrombin, the thrombin receptor-activating peptide SFLLRN, bradykinin, substance P, and calcimycin produced dose-dependent relaxations. These relaxations were not inhibited by prior incubation with pertussis toxin, but were abolished upon the addition of charybdotoxin plus apamin. Relaxations to the α2-adrenergic agonist UK14304 and those to serotonin were abolished in the presence of indomethacin and L-NAME.

Conclusion: Unlike nitric oxide-mediated relaxations, EDHF-mediated relaxations of pig coronary arteries do not involve pertussis toxin-sensitive pathways and are Gi/o protein independent.

Keywords: endothelium-derived hyperpolarizing factor; pertussis toxin; Gi/o protein; pig coronary artery

¹This study is supported in part by a CRCG grant from the University of Hong Kong (No 21374077) and in part by departmental funds.
²The preliminary data of this study have been presented at the Symposium on Mechanism of
Vasodilatation and EDHF 2005, Antwerp 31 May_June 4 2005 and published as a conference abstract in J Vasc Res 2005; 42 Suppl 1: 12 S2010.

⁵Correspondence to Dr Kwok Fu Jacobus NG.
Fax 852-2855-1654.
E-mail jkfng@hkucc.hku.hk
Received 2008-05-30 Accepted 2008-10-09

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