NG‐hydroxy‐L‐arginine prevents the haemodynamic effects of nitric oxide synthesis inhibition in the anaesthetized rat

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 NG‐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 NG‐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.