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 of genetically salt-sensitive, hypertension-prone rats. We have previously reported that renal xanthine oxidoreductase (XOR) activity is increased in hypertension-prone rats, and even more markedly in salt-induced experimental hypertension. XOR is an enzyme involved in purine metabolism, converting ATP 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 NaCl in the chow), for three weeks with a nitric oxide synthase (NOS) inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 20mg/kg/d). L-NAME treatment induced renal XOR activity by 14 to 37 % (P<0.001), depending on the intake level of salt. Increased salt intake was no more able to aggravate L-NAME induced hypertension, but it did further increase the renal XOR activity (p<0.05). Treatment of SHRs with a nitric oxide donor, isosorbide-5-mononitrate (60-70 mg/kg/d for 8 weeks), markedly attenuated the salt-enhanced hypertension without a clear effect on renal XOR activity. Thus, the results indicate that the NO concentration needed to inhibit XOR is supra-physiological, and suggest that renal NO production is not impaired in the SHR model of hypertension.
Laakso
J
J
Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. juha.laakso@helsinki.fi
Vaskonen
T
T
Mervaala
E
E
Vapaatalo
H
H
Lapatto
R
R
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006973:Hypertension / Q000201:enzymology*; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D017673:Sodium Chloride, Dietary; D019001:Nitric Oxide Synthase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate; D019331:NG-Nitroarginine Methyl Ester