Time-dependent increase in nitric oxide formation concurrent with vasodilation induced by sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-N-acetylpenicillamine but not by glyceryl trinitrate.
Nitrovasodilators is a term used to describe a diverse group of agents believed to exert their vasodilator effect by a common mechanism, namely formation of nitric oxide. The objective of the present study was to test this concept by comparing the magnitude of nitric oxide formation from four representative nitrovasodilators incubated in the presence of rabbit aortic strips (RAS) with the magnitude of nitrovasodilator-induced relaxation of RAS, over the time course of relaxation. The RAS were incubated in anaerobic condition with 100 microM either sodium nitroprusside, glyceryl trinitrate (GTN), 3-morpholinosydnonimine, or S-nitroso-N-acetylpenicillamine in Krebs' solution. Relaxation of RAS by each of the four drugs started at approximately 10 sec and increased with incubation time. Formation of nitric oxide was measurable using a chemiluminescence-headspace-gas method at 0.5 min with sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-N-acetylpenicillamine, and formation increased concurrently with relaxation of RAS. In contrast, formation of nitric oxide from GTN was not measurable until 5 min, at which time GTN-induced relaxation of RAS was nearly complete. These data support the concept that sodium nitroprusside, 3-morpholinosydnonimine, and S-nitroso-N-acetylpenicillamine are nitrovasodilator drugs acting via formation of nitric oxide. However, the present study suggests that the mechanism of action for GTN-induced vasodilation may involve the formation of a nitric oxide-adduct, such as a nitrosothiol, rather than nitric oxide per se.
Marks
G S
GS
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
McLaughlin
B E
BE
Jimmo
S L
SL
Poklewska-Koziell
M
M
Brien
J F
JF
Nakatsu
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D026423:S-Nitroso-N-Acetylpenicillamine; D013997:Time Factors; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D026423:S-Nitroso-N-Acetylpenicillamine; D008981:Molsidomine; D005996:Nitroglycerin; D010396:Penicillamine