Differential effects of L-NAME on blood pressure and heart rate responses to acetylcholine and bradykinin in cynomolgus primates.
NG-nitro-L-arginine methyl ester (L-NAME) has been reported to have variable effects on the vasodilator response to acetylcholine (ACh) and bradykinin (BK) in vivo. Whether administration of L-NAME affects mean arterial pressure (MAP) or heart rate (HR) responses to ACh or BK was examined in conscious cynomolgus primates. ACh (0.1-10 micrograms/kg i.v.) lowered MAP by 6% to 37%, responses which were inhibited (25-62%) in the presence of L-NAME (1-100 mg/kg i.v.). Although L-NAME increased MAP similarly at doses of 10 and 100 mg/kg, only the 100-mg/kg dose inhibited the hypotensive responses induced by the higher doses of ACh. By comparison, nitroprusside (5 micrograms/kg i.v.)-induced hypotensive responses were not inhibited by L-NAME. Phenylephrine (20 micrograms kg-1 min-1 i.v.) increased MAP and lowered HR to levels statistically similar to that of L-NAME but did not alter ACh-induced hypotensive responses. ACh dose-dependently decreased HR, both in the absence and presence of L-NAME or phenylephrine. In pentobarbital-anesthetized monkeys, ACh-induced hypotensive responses were inhibited by 75% to 94% in the presence of L-NAME; BK (0.3-1 microgram/kg i.v.) responses were only modestly affected (< or = 50%). Therefore, in conscious primates, L-NAME affects the basal release of nitric oxide (NO) at lower doses than those required to inhibit its release stimulated by ACh. Also, L-NAME does not appear to act as a cholinergic antagonist or affect the functional mechanisms that control baroreflex responses.(ABSTRACT TRUNCATED AT 250 WORDS)
Weldon
S M
SM
Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut.
Winquist
R J
RJ
Madwed
J B
JB
D000109:Acetylcholine / Q000494:pharmacology*; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008252:Macaca fascicularis; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D010656:Phenylephrine / Q000494:pharmacology; D014851:Wakefulness
D010656:Phenylephrine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester