Increased renal vascular resistance in zinc-deficient rats: role of nitric oxide and superoxide.
1. Zinc deficiency (ZD) induces many kinds of pathological states. However, the effects of ZD on haemodynamics remain unclear. In the present study, we measured mean blood pressure (BP) and renal blood flow (RBF) under anaesthesia and calculated renal vascular resistance (RVR) from these parameters in rats maintained on a ZD diet (0.5 p.p.m. zinc) for 4 weeks. 2. Zinc deficiency did not change mean BP, but significantly reduced RBF and increased RVR (each P < 0.01). In addition, these effects of ZD were reversible. 3. Because Cu/Zn superoxide dismutase (SOD) is a zinc-containing enzyme and superoxide is a potent scavenger of nitric oxide (NO), a vasodilator, we hypothesized that one of the mechanisms by which ZD increases RVR is by decreasing NO bioavailability by the enhanced formation of superoxide due to low Cu/Zn SOD activity. To test this hypothesis, we observed the roles of NO and superoxide in the mechanism, after having confirmed the low activity of Cu/Zn SOD in the kidneys of ZD rats. 4. Administration of the SOD mimetic tempol (5 mg/kg per min) decreased RVR to a significantly greater extent in ZD rats compared with control, suggesting that superoxide was responsible for the mechanism. Low doses of the NO donor sodium nitroprusside (SNP; 2.0 micro g/kg per min, continuous) decreased RVR to a significantly smaller extent in ZD rats compared with control, whereas a high dose of SNP (0.75 mg/kg, bolus) decreased RVR to a significantly greater extent in ZD rats compared with control, suggesting that the mechanism includes an inhibition of NO activity in ZD, which is most likely to be a scavenging of NO by the activated superoxide. 5. In summary, ZD may increase RVR. The mechanism probably includes changes in NO and superoxide activities.
Kurihara
Nobutaka
N
Department of Hygiene and Preventive Medicine, Saitama Medical School, Saitama, Japan. kurihara@saitma-med.ac.jp
Yanagisawa
Hiroyuki
H
Sato
Masamichi
M
Tien
Chang-Kuen
CK
Wada
Osamu
O
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000172:deficiency*
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D013481:Superoxides; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D015032:Zinc