Differential effects of nitric oxide synthesis inhibitors on vascular resistance and responses to acetylcholine in cats.
The effects of dose and the duration of treatment with N omega-nitro-L-arginine (L-NNA) and N omega-nitro-L-arginine methyl ester (L-NAME) on vascular resistance and the vasodilator response to acetylcholine (ACh) were investigated in the hindquarters vascular bed of the cat under constant flow conditions. L-NNA and L-NAME increase perfusion pressure and reduce vasodilator responses to ACh in the hindquarters vascular bed; however, the dose and time of exposure required to produce these effects are different. When L-NNA (2.5-5 mg/min) was infused into the hindquarters vascular bed, the increase in perfusion pressure was observed 10 min after onset of the infusion, at which time responses to ACh were not changed. The time of exposure for 50% of the maximal change in hindquarters perfusion pressure was significantly less than the time of exposure for 50% of the maximal decrease in the vasodilator response to ACh during infusion of L-NNA. A similar pattern was observed after the intravenous administration of 3-300 mg/kg L-NAME, while 1 mg/kg L-NAME produced a large but submaximal pressor response and lesser decreases in responses to ACh. The arginine analogues did not completely inhibit the vasodilator response to ACh in the hindquarters vascular bed, with a 30-fold increase in dose producing no additional blockade; however, L-NNA completely inhibited the relaxant response to ACh in the isolated aorta of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)
Bellan
J A
JA
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
McNamara
D B
DB
Kadowitz
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb / Q000098:blood supply; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012039:Regional Blood Flow; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester