Superoxide contributes to development of salt sensitivity and hypertension induced by nitric oxide deficiency.
This study was performed to examine the role of superoxide (O2-) in the development of salt sensitivity and hypertension induced by inhibition of nitric oxide (NO) generation. Male Sprague-Dawley rats were fed with diet containing either normal salt (NS) (0.4% NaCl) or high salt (HS) (4% NaCl). These rats were treated with or without an NO synthase inhibitor, nitro-L-arginine methylester (L-NAME) (15 mg/kg/d) and O2- scavenger, tempol (30 mg/kg per day) in the drinking water for 4 weeks. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography and urine collection was performed during the course of experimental periods. At the end of 4 weeks, L-NAME treatment resulted in greater increases in SBP in HS rats (127+/-2 to 172+/-3 mm Hg; n=8) than in NS rats (130+/-2 to 156+/-2 mm Hg; n=9). Co-administration of tempol with L-NAME markedly attenuated these SBP responses to a similar level in both HS (128+/-3 to 147+/-2 mm Hg; n=8) and NS rats (126+/-2 to 142+/-3 mm Hg; n=8). Urinary 8-isoprostane excretion (UIsoV) increased in response to L-NAME treatment that was higher in HS (10.6+/-0.5 to 21.5+/-0.8 ng/d) than in NS rats (10.8+/-0.7 to 16.9+/-0.6 ng/d). Co-treatment with tempol completely abolished these UIsoV responses to L-NAME in both HS and NS rats but did not alter urinary H2O2 excretion rate. The decreases in urinary nitrate/nitrite excretion in response to L-NAME treatment were not altered by co-administration of tempol in both HS and NS rats. These data suggest that enhancement of O2- activity during NO inhibition contributes to the development of salt sensitivity that is associated with NO-deficient hypertension.
Kopkan
Libor
L
Department of Physiology, Tulane Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA, USA.
Majid
Dewan S A
DS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004231:Diuresis; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000652:urine; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000652:urine; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*
D003497:Cyclic N-Oxides; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D013481:Superoxides; C075750:8-epi-prostaglandin F2alpha; D009569:Nitric Oxide; D015237:Dinoprost; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester