Inhibition of nitric oxide synthase induces renal xanthine oxidoreductase activity in spontaneously hypertensive rats

The kidney function plays a crucial role in the salt-induced hypertension o f genetically salt-sensitive, hypertension-prone rats. We have previously r eported that renal xanthine oxidoreductase (XOR) activity is increased in h ypertension-prone rats, and even more markedly in salt-induced experimental hypertension. XOR is an enzyme involved in purine metabolism, converting A TP metabolites hypoxanthine and xanthine to uric acid. Because the possible involvement of XOR in nitric oxide metabolism has gained recent interest, we determined renal XOR activity after treating spontaneously hypertensive rats (SHRs), kept on different salt intake levels (0.2, 1.1 and 6.0 % of Na Cl in the chow), for three weeks with a nitric oxide synthase (NOS) inhibit or, N-omega-nitro-L-arginine methyl ester (L-NAME, 20mg/kg/d). L-NAME treat ment induced renal XOR activity by 14 to 37% (P<0.001), depending on the in take level of salt. Increased salt intake was no more able to aggravate L-N AME induced hypertension, but it did further increase the renal XOR activit y (p<0.05). Treatment of SHRs with a nitric oxide donor, isosorbide-5-monon itrate (60-70 mg/kg/d for 8 weeks), markedly attenuated the salt-enhanced h ypertension without a clear effect on renal XOR activity. Thus, the results indicate that the NO concentration needed to inhibit XOR is supra-physiolo gical, and suggest that renal NO production is not impaired in the SHR mode l of hypertension.