Endothelium-derived hyperpolarizing factor mediated relaxations in pig coronary arteries do not involve Gi/o proteins.
OBJECTIVE
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 degrees and continuously aerated with 95%O2 and 5% CO2. Isometric tension was measured during contractions to prostaglandin F2alpha in the presence of indomethacin and N(omega)- 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 alpha2-adrenergic agonist UK14304 and those to serotonin were abolished in the presence of indomethacin and L-NAME.


CONCLUSIONS
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.
Ng
Kwok Fu Jacobus
KF
Department of Anaesthesiology, The University of Hong Kong, Hong Kong, China. jkfng@hkucc.hku.hk
Leung
Susan Wai Sum
SW
Man
Ricky Ying Keung
RY
Vanhoutte
Paul M
PM
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001685:Biological Factors / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D006490:Hemostatics / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D034421:Sus scrofa; D013917:Thrombin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D006490:Hemostatics; D007476:Ionophores; D009498:Neurotoxins; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; C082835:thrombin receptor peptide (42-47); D018999:Charybdotoxin; D001030:Apamin; D012701:Serotonin; D013373:Substance P; D000001:Calcimycin; D007650:Ketanserin; D015237:Dinoprost; D037342:Pertussis Toxin; D013917:Thrombin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester