High salt (HS) intake can lead to hypertension, probably the result of the predominance of vasoconstrictor reactive oxygen species over vasodilator nitric oxide (NO). We aimed to examine if the supposed NO deficiency and the resultant blood pressure increase could be corrected by supplementation of L-arginine, the substrate, and tetrahydrobiopterin (BH4), a co-factor of NO synthases. Wistar rats without known genetic background of salt sensitivity were exposed to HS diet (4%Na) for 10 or 26 days, without or with supplementation with oral L-arginine, 1.4 mg/kg b.w. daily, alone or together with intraperitoneal BH4, 10 mg/kg daily. Systolic blood pressure (SBP, tail-cuff method) was measured repeatedly and found to increase ~40 mmHg after 26 days; L-arginine and BH4 did not significantly attenuate this increase. At the end of chronic studies, in anaesthetized rats the diet- and treatment-induced changes in renal haemodynamics were assessed. HS diet selectively decreased (-30%, P < 0.03) the inner medullary blood flow (IMBF, laser-Doppler flux) without changing total or cortical renal perfusion. Arginine supplementation tended to raise all renal circulatory parameters, and distinctly increased IMBF, to 61% above the HS diet level (P < 0.05). In conclusion, unlike in confirmed genetically determined salt-dependent hypertension, L-arginine and BH4 supplementation failed to attenuate the SBP increase observed after exposure to HS diet. On the other hand, arginine increased total and regional renal perfusion, especially IMBF. This suggests that the delivery of arginine increased intrarenal NO synthesis, an action of renoprotective potential which presumably countered the harmful influence of the local tissue oxidative stress.