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N G ‐hydroxy‐L‐arginine prevents the haemodynamic effects of nitric oxide synthesis inhibition in the anaesthetized rat
Author(s) -
Walder Claire E.,
Thiemermann Christoph,
Vane John R.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb12770.x
Subject(s) - nitric oxide , arginine , renal blood flow , hemodynamics , vascular resistance , chemistry , bolus (digestion) , endocrinology , mean arterial pressure , medicine , blood pressure , nitroarginine , renal circulation , nitric oxide synthase , biochemistry , amino acid , heart rate
1 We have investigated the effects of l ‐hydroxy‐ l ‐arginine ( l ‐HOArg), an intermediate in the biosynthesis of nitric oxide (NO) from l ‐arginine ( l ‐Arg), on the haemodynamic effects (systemic blood pressure and renal blood flow) of the NO synthesis inhibitor N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME) in the anaesthetized rat. 2 l ‐Arg or l ‐HOArg (3 mg kg −1 min −1 ), but not d ‐arginine ( d ‐Arg) or N G ‐hydroxy‐ d ‐arginine ( d ‐HOArg), elicited a slight but significant increase in total renal blood flow (RBF) of 11 ± 2% and 11 ± 1%. Since mean arterial blood pressure (MAP) did not change this dose of l ‐Arg or l ‐HOArg resulted in a reduced renal vascular resistance (RVR) of the same magnitude. 3 Bolus injections of l ‐NAME, at 0.3 or 1 mg kg −1 i.v., produced a significant fall in RBF of 11 ± 2% and 32 ± 5% and an increase in MAP of 7 ± 3 mmHg and 22 ± 5 mmHg, respectively. Consequently, RVR was elevated by 21 ± 5% and 52 ± 10%. 4 l ‐Arg or l ‐HOArg (3 mg kg −1 min −1 ) reduced the l ‐NAME‐induced (0.3 or 1 mg kg −1 ) falls in RBF and increases in RVR by more than 65%. Neither d ‐Arg nor d ‐HOArg (3 mg kg −1 min −1 ) had any significant effect on the changes in RBF or RVR induced by l ‐NAME. 5 l ‐Arg or l ‐HOArg (3 mg kg −1 min −1 ) attenuated the pressor effect of l ‐NAME (3 mg kg −1 ) by 73% and 64%, respectively, while neither the d ‐isomer of arginine nor hydroxyarginine had any effect. 6 These results demonstrate that l ‐HOArg antagonizes the haemodynamic effects of NO‐biosynthesis inhibition in vivo , thus supporting the hypothesis that l ‐HOArg is an intermediate in the formation of NO from l ‐Arg.