Cardiovascular responses to long-term blockade of nitric oxide synthesis.
The goal of this study was to determine if there is a basal release of nitric oxide that affects long-term arterial pressure regulation in dogs. Studies were conducted over a 23-day period in eight conscious dogs with indwelling catheters. Nitric oxide synthesis was blocked by continuous intravenous infusion of nitro-L-arginine-methyl ester at 37.1 nmol/kg per minute for 11 days. Arterial pressure increased to 120 +/- 4% of control on the first day, decreased for a few days, and then increased to a maximum value of 122 +/- 6% of control on day 7. Bradycardia was sustained throughout the entire nitro-arginine period. Blockade of nitric oxide synthesis was evidenced by attenuated pressure and flow responses to systemic acetylcholine infusion. The pressor response to phenylephrine was increased for only 1 day, and the hypotensive effects of nitroprusside were enhanced. Also, the variability of arterial pressure was significantly increased during nitro-arginine. Sodium and water balances were positive the first day of nitro-arginine infusion but were unchanged for the entire nitro-arginine period. In conclusion, the data suggest that blockade of the basal release of nitric oxide in dogs causes an increase in the long-term level of arterial pressure without any sustained sodium or water retention.
Manning
R D
RD
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505.
Hu
L
L
Mizelle
H L
HL
Montani
J P
JP
Norton
M W
MW
D000109:Acetylcholine / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000209:etiology*; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D011311:Pressoreceptors / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000493:pharmacokinetics; D014882:Water-Electrolyte Balance / Q000187:drug effects
D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D003404:Creatinine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D000109:Acetylcholine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester