An analysis of renal nitric oxide contribution to hyperfiltration in diabetic rats.
We have investigated whether nitric oxide (NO) generation is increased in diabetes and whether specific NO synthase (NOS) isoforms are up-regulated in 4-week diabetic male Wistar rats. Glomerular filtration rate (GFR), kidney weight, and urinary nitrate (NOx) generation were measured in the following groups (n = 6): normal control animals, diabetic animals, diabetic animals given L -NIL (a selective iNOS inhibitor)(D + L -NIL), diabetic animals given L -NAME (a nonselective NOS inhibitor)(D + L -NAME), and control animals given L -NAME (C + L -NAME). Diabetes increased GFR (0.78 +/- 0.05 mL/min/100 g body wt vs 1.49 +/- 0.07 mL/min/100 g body wt, P <.01). L -NIL did not affect hyperfiltration, while L -NAME decreased GFR to values that were lower than those in normal control animals, a response identical to that in non-diabetic control rats. L -NIL did not affect urinary NOx values, but L -NAME completely abolished the increase in urinary nitrates. Kidney weight was not affected by L -NIL, but L -NAME significantly attenuated kidney growth. Inducible NOS (iNOS) and endothelial NOS (eNOS) mRNA levels measured by reverse transcription-polymerase chain reaction in diabetic rats were not changed as compared with levels in controls. Cyclic guanosine monophosphate responses to carbachol (an index of eNOS activity) in glomeruli from diabetic rats were significantly reduced as compared with those in controls, and guanylate cyclase responses to sodium nitroprusside were significantly decreased. Therefore, renal NO generation, at least via eNOS and iNOS, is not the primary cause of glomerular hyperfiltration in diabetes.
Schwartz
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Division of Nephrology and Hypertension, University of California San Diego, and the Veterans Affairs Medical Center, San Diego, CA, USA.
Schwartz
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Blantz
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D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D006162:Guanylate Cyclase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D009599:Nitroprusside; D009569:Nitric Oxide; D002217:Carbachol; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester