Inhibition of locally produced nitric oxide resets tubuloglomerular feedback mechanism. 1994

C Thorup, and A E Persson
Department of Physiology and Biophysics, Lund University, Sweden.

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.

UI MeSH Term Description Entries
D007678 Kidney Glomerulus A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. Glomerulus, Kidney
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008138 Loop of Henle The U-shaped portion of the renal tubule in the KIDNEY MEDULLA, consisting of a descending limb and an ascending limb. It is situated between the PROXIMAL KIDNEY TUBULE and the DISTAL KIDNEY TUBULE. Ascending Limb of Loop of Henle,Descending Limb of Loop of Henle,Henle Loop
D008297 Male Males
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D010477 Perfusion Treatment process involving the injection of fluid into an organ or tissue. Perfusions
D000594 Amino Acid Oxidoreductases A class of enzymes that catalyze oxidation-reduction reactions of amino acids. Acid Oxidoreductases, Amino,Oxidoreductases, Amino Acid
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001120 Arginine An essential amino acid that is physiologically active in the L-form. Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate

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