Inhibition of locally produced nitric oxide resets tubuloglomerular feedback mechanism.
This study was designed to compare the effects of systemic and intratubular infusions of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine (L-NNA) on the tubuloglomerular feedback (TGF) mechanism in anesthetized rats. We recently showed that intravenous infusion of L-NNA led to increases in mean arterial blood pressure (Pa), proximal tubular stop-flow pressure (Psf), and enhanced TGF sensitivity and reactivity. To avoid major systemic effects, in this study TGF was studied after intratubular NO inhibition. Intratubular infusion of L-NNA (10(-3) M) yielded similar results as shown with intravenous infusion, without systemic effects. TGF sensitivity and reactivity were increased, indicated by decreased turning point (TP) from 19.8 +/- 1.0 to 15.2 +/- 0.7 nl/min and increased delta Psf from 10.0 +/- 0.8 to 23.9 +/- 1.9 mmHg (24.3 vs. 59.1%). L-NNA at a concentration of 10(-4) M showed significant changes in both TP (from 20.9 +/- 1.1 to 17.8 +/- 1.0 nl/min) and delta Psf (from 7.6 +/- 0.6 to 13.9 +/- 0.7 mmHg), whereas 10(-5) M only increased delta Psf (9.7 +/- 1.0 vs. 12.1 +/- 1.1 mmHg). However, at low tubular perfusion rates Psf was not influenced by L-NNA. The early proximal flow rate (EPFR) showed no change at low tubular perfusion rates with L-NNA. At maximal TGF activation (40 nl/min), delta EPFR was increased from 34% in control to 62%. Our results suggest that NO not only regulates glomerular capillary pressure but also decreases the sensitivity of the TGF mechanism.
Thorup
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Department of Physiology and Biophysics, Lund University, Sweden.
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008138:Loop of Henle / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases