Effect of pertussis toxin and the cGMP lowering agent LY83583 on the relaxation induced by nitrates in isolated bovine mesenteric artery. A comparison between glyceryl trinitrate, isosorbide dinitrate and isosorbide 5-mononitrate.
The effect of pertussis toxin (PTX) and the cyclic GMP-lowering agent LY83583 on the relaxatory response induced by glyceryl trinitrate (GTN), isosorbide dinitrate (ISDN) and isosorbide-5-mononitrate (ISMN) in bovine mesenteric artery was investigated. Pretreatment with PTX (100 ng/ml; 2h) induced a 100-fold right shift of the concentration-effect curve for GTN, while no effect on the relaxatory response elicited by ISDN and ISMN was seen 10 microM LY83583 markedly reduced the relaxatory effect of all the organic nitroesters. Based on the different sensitivity towards PTX it is suggested that GTN induces vascular smooth muscle relaxation by a partly different mechanism than ISDN and ISMN. However, cGMP seems to play a crucial role in mediating the relaxatory response of all the tested organic nitroesters since LY83583 profoundly suppressed the relaxatory response.
Axelsson
K L
KL
Department of Pharmacology, Linköping University, Sweden.
Ahlner
J
J
Torfgård
K
K
D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009566:Nitrates / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D037342:Pertussis Toxin; D014655:Vascular Resistance / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000634:Aminoquinolines; D009566:Nitrates; D010566:Virulence Factors, Bordetella; C041715:6-anilino-5,8-quinolinedione; D037342:Pertussis Toxin; D005996:Nitroglycerin; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate