Superoxide formation and interaction with nitric oxide modulate systemic arterial pressure and renal function in salt-depleted dogs.
To determine the role of superoxide (O(2)(-)) formation in the kidney during alterations in the renin-angiotensin system, we evaluated responses to the intra-arterial infusion of an O(2)(-) - scavenging agent, tempol, in the denervated kidney of anesthetized salt-depleted (SD, n=6) dogs and salt-replete (SR, n=6) dogs. As expected, basal plasma renin activity was higher in SD than in SR dogs (8.4 +/- 1.0 vs. 2.3 +/- 0.6 ng angiotensin 1/ml/hr). Interestingly, the basal level of urinary F(2)-isoprostanes excretion (marker for endogenous O(2)(-) activity) relative to creatinine (Cr) excretion was also significantly higher in SD compared to SR dogs (9.1 +/- 2.8 vs. 1.6 +/- 0.4 ng F(2)-isoprostanes/mg of Cr). There was a significant increase in renal blood flow (4.3 +/- 0.5 to 4.9 +/- 0.6 ml/min/g) and decreases in renal vascular resistance (38.2 +/- 5.8 to 33.2 +/- 4.7 mm Hg/ml/min/g) and mean systemic arterial pressure (148 +/- 6 to 112 +/- 10 mm Hg) in SD dogs but not in SR dogs during infusion of tempol at 1 mg/kg/min for 30 mins. Glomerular filtration rate and urinary sodium excretion (U(Na)V) did not change significantly during tempol infusion in both groups of dogs. Administration of the nitric oxide synthase inhibitor nitro-L-arginine (50 mug/kg/min) during tempol infusion caused a reduction in U(Na)V in SR dogs (47% +/- 12%) but did not cause a decrease in SD dogs. These data show that low salt intake enhances O(2)(-) activity that influences renal and systemic hemodynamics and thus may contribute to the regulation of arterial pressure in the salt-restricted state.
Dutta
Utpal K
UK
Department of Physiology, SL 39, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Lane
Jason
J
Roberts
L Jackson
LJ
Majid
Dewan S A
DS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D028421:Isoprostanes / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D012964:Sodium / Q000652:urine; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D003497:Cyclic N-Oxides; D028421:Isoprostanes; D013113:Spin Labels; D013481:Superoxides; D019335:Nitroarginine; D009569:Nitric Oxide; D012964:Sodium; D019001:Nitric Oxide Synthase; D012083:Renin; C001803:tempol