Electrical field stimulation causes endothelium-dependent and nitric oxide-mediated relaxation of pulmonary artery.
The objective of this study was to ascertain the mechanism by which electrical field stimulation (EFS) of bovine pulmonary arterial rings causes endothelium-dependent smooth muscle relaxation. Like acetylcholine-elicited relaxation, EFS-elicited relaxation was endothelium-dependent and accompanied by accumulation of guanosine 3',5'-cyclic monophosphate (cGMP) in the vascular smooth muscle. Relaxation in response to EFS was unaltered by tetrodotoxin, guanethidine, atropine, propranolol, chlorpheniramine, cimetidine, indomethacin, aminophylline, alpha, beta-methylene ATP, nifedipine, capsaicin, and certain antioxidants and free radical scavengers. Thus the relaxation was not neurogenically mediated and was not attributed to free radical formation during EFS. Like nitric oxide-elicited relaxation, EFS-elicited relaxation was antagonized by oxyhemoglobin and methylene blue. Relaxation was also antagonized by the three NG-substituted L-arginine analogues: NG-methyl-L-arginine, NG-nitro-L-arginine, and NG-amino-L-arginine. NG-amino-L-arginine also inhibited the tissue cGMP accumulation in response to EFS. The inhibitory effect of the NG-substituted L-arginine analogues was reversed by addition of excess L-arginine but not D-arginine. Relaxation in response to EFS was dependent on the presence of extracellular calcium and intracellular calmodulin, as removal of extracellular calcium or addition of trifluoperazine nearly abolished relaxation. EFS-elicited relaxation was inhibited also by tetraethylammonium chloride and elevated extracellular potassium concentration. These observations indicate that EFS-elicited relaxation of bovine pulmonary artery is mediated by neuronally independent, but endothelium- and calcium-dependent, stimulation of nitric oxide and cGMP formation.
Buga
G M
GM
Department of Pharmacology, University of California School of Medicine, Los Angeles 90024.
Ignarro
L J
LJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006152:Cyclic GMP / Q000096:biosynthesis; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; C063904:N(G)-aminoarginine; D001120:Arginine; D006152:Cyclic GMP; D002118:Calcium