Nitric oxide antagonizes the actions of angiotensin II to enhance tubuloglomerular feedback responsiveness.
The present study was designed to investigate whether nitric oxide (NO) antagonizes angiotensin II (Ang II) in modulating the tubuloglomerular feedback (TGF) system. Maximum TGF responses were assessed by evaluating stop-flow pressure (SFP) responses to late proximal perfusion with artificial tubular fluid (40 nl/min). Peritubular capillary (PTC) infusion of 10(-3) M NG-L-arginine (NLA) at a rate of 20 nl/min, and infusion of 10(-7) and 10(-6) M Ang II at rates that did not decrease SFP under conditions of zero flow to the macula densa (resting SFP), augmented maximum SFP feedback responses to 12.0 +/- 1.7, 12.1 +/- 2.4 and 16.9 +/- 3.0 mm Hg, respectively (all P < 0.01 vs. control response). Combined PTC infusion of NLA and 10(-7) M Ang II at a rate of 20 nl/min resulted in decreases in resting SFP in 7 of the 12 nephrons studied. When the infusion rate was decreased to 15 +/- 3 nl/min, concomitant PTC infusion of NLA and 10(-7) M Ang II was associated with a tremendous increase in maximum TGF responses (23.8 +/- 3.9 mm Hg; P < 0.01 vs. responses during PTC NLA or Ang II) in the absence of a decrease in resting SFP. During AT1 receptor blockade using losartan, SFP feedback responses were attenuated to 1.6 +/- 0.6 mm Hg and PTC infusion of NLA only augmented TGF responses to 3.8 +/- 1.0 mm Hg. These results strongly suggest that local NO antagonizes Ang II with respect to the regulation of TGF responsiveness. Disruption of this balance by NO synthesis inhibition strongly potentiates TGF-independent and TGF-dependent actions of Ang II on the preglomerular vasculature.
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
B
B
Braam
H A
HA
Koomans
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002196:Capillaries; D005246:Feedback / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007267:Injections; D007275:Injections, Intravenous; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000098:blood supply / Q000502:physiology*; D019808:Losartan; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology
D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019808:Losartan