Endothelium-derived hyperpolarizing factor mediated relaxations in pig coronary arteries do not involve Gi/o proteins
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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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.