Pressor effects of L and D enantiomers of NG-nitro-arginine in conscious rats are antagonized by L- but not D-arginine.
The effects of NG-nitro-L-arginine (L-NNA) and NG-nitro-D-arginine (D-NNA) on mean arterial pressure (MAP) were studied in conscious, unrestrained rats. I.v. bolus of either L-NNA (1-64 mg/kg) or D-NNA (2-64 mg/kg) dose dependently increased MAP to similar maximum values of 55 +/- 7 and 52 +/- 4 mm Hg and with ED50 values of 4.0 +/- 0.9 and 8.9 +/- 1.2 mg/kg (P less than 0.05), respectively. The time course of the MAP response to a single dose (32 mg/kg i.v. bolus) of L-NNA and D-NNA were also obtained. The pressor effects of L-NNA and D-NNA each lasted greater than 2 h with the rise phase t 1/2 of 5 and 27 min (P less than 0.05), respectively. I.v. infusions (10 mg/kg per min) of L-arginine (L-Arg) and D-arginine (D-Arg) did not alter the pressor response to noradrenaline nor angiotensin II. L-Arg but not D-Arg attenuated the pressor responses to both L-NNA and D-NNA. Therefore, both L-NNA and D-NNA are efficacious and long-lasting pressor agents; the pressor effects of both can be antagonized by L-Arg but not D-Arg. Our results suggest that the pressor effects of both L-NNA and D-NNA involve the L-Arg/nitric oxide pathway.
Wang
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Zhou
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Pang
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019335:Nitroarginine; D009904:Optical Rotation; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D019335:Nitroarginine; D001120:Arginine