Abstract
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 °C and continuously aerated with 95%O2 and 5% CO2. Isometric tension was measured during contractions to prostaglandin F2α in the presence of indomethacin and Nω-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.
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This study is supported in part by a CRCG grant from the University of Hong Kong (No 21374077) and in part by departmental funds.
The 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.
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NG, K., Leung, S., Man, R. et al. Endothelium-derived hyperpolarizing factor mediated relaxations in pig coronary arteries do not involve Gi/o proteins. Acta Pharmacol Sin 29, 1419–1424 (2008). https://doi.org/10.1111/j.1745-7254.2008.00905.x
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DOI: https://doi.org/10.1111/j.1745-7254.2008.00905.x
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