Superoxide anion curbs nitric oxide modulation of afferent arteriolar ANG II responsiveness in diabetes mellitus.
Experiments were performed to test the hypothesis that the impact of endogenous nitric oxide (NO) on ANG II-induced renal arteriolar constriction is reduced in rats with insulin-dependent diabetes mellitus (65 mg/kg streptozotocin; STZ). Arteriolar diameter responses to exogenous ANG II were quantified before and during NO synthase inhibition (100 microM N(omega)-nitro-L-arginine; L-NNA) by using the in vitro blood-perfused juxtamedullary nephron technique. Afferent arteriolar lumen diameter averaged 20.7 +/- 2.0 micrometer in Sham kidneys and 25.9 +/- 1.3 micrometer in STZ kidneys (P < 0.05). Efferent arteriolar diameter did not differ between Sham and STZ rats. In kidneys from Sham rats, afferent and efferent arteriolar responses to ANG II (0.1-10.0 nM) were exaggerated significantly by L-NNA. L-NNA also augmented efferent arteriolar ANG II responses in kidneys from STZ rats (high-glucose bath) but did not alter ANG II responses in afferent arterioles from STZ rats. L-NNA also accentuated efferent, but not afferent, arteriolar ANG II responses in STZ kidneys during acute restoration of bath glucose to normal levels. Superoxide dismutase (150 U/ml) restored the ability of L-NNA to allow exaggerated afferent arteriolar responses to ANG II in kidneys from STZ rats. These observations indicate that superoxide anion suppresses the modulatory influence of endogenous NO on ANG II-induced afferent arteriolar constriction in diabetes mellitus.
Schoonmaker
G C
GC
Department of Physiology, University of Nebraska College of Medicine, Omaha, Nebraska 68198-4575, USA.
Fallet
R W
RW
Carmines
P K
PK
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; D009569:Nitric Oxide; D013311:Streptozocin; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005947:Glucose