Difference in effect of inhibitors of energy metabolism on endothelium-dependent relaxation of rat pulmonary artery and aorta.
Previous studies have suggested that systemic artery endothelial cell production of the nitrovasodilator endothelium-derived relaxing factor (EDRF) is dependent upon oxidative energy production. This study was undertaken to test if pulmonary artery (PA) EDRF has a similar requirement for oxidative phosphorylation. The effects of inhibitors of oxidative phosphorylation and glycolysis on endothelium-dependent relaxation were studied in rat aortic and PA rings. In aortic rings, 0.1 microM rotenone and 0.1 microM antimycin A, and, to a lesser extent, 50 mM 2-deoxyglucose, inhibited endothelium-dependent relaxation to acetylcholine and adenosine diphosphate. Relaxation to the receptor-independent calcium ionophore A23187 was less severely affected, and relaxation to the direct smooth muscle dilator sodium nitroprusside was unaffected. The inhibitors had much less effect on PA relaxation, decreasing the potency but not the efficacy of the endothelium-dependent dilators. These results suggest that the dependence on oxidative energy production for endothelium-dependent relaxation may differ between the systemic and pulmonary vascular beds, and that in pulmonary arterial endothelium, oxidative energy production may not be required for receptor-mediated production and/or release of EDRF. The resistance of PA endothelium to decreases in oxidative energy production may contribute to the normally low tone maintained in this circuit in vivo.
Rodman
D M
DM
Division of Pulmonary Sciences, University of Colorado, Health Sciences Center, Denver.
Mallet
J
J
McMurtry
I F
IF
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D012402:Rotenone; D000968:Antimycin A; D003847:Deoxyglucose