| Shear stress increases nitric oxide production in thick ascending limbs. | |
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MedLine Citation:
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PMID: 20719980 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We showed that luminal flow stimulates nitric oxide (NO) production in thick ascending limbs. Ion delivery, stretch, pressure, and shear stress all increase when flow is enhanced. We hypothesized that shear stress stimulates NO in thick ascending limbs, whereas stretch, pressure, and ion delivery do not. We measured NO in isolated, perfused rat thick ascending limbs using the NO-sensitive dye DAF FM-DA. NO production rose from 21 ± 7 to 58 ± 12 AU/min (P < 0.02; n = 7) when we increased luminal flow from 0 to 20 nl/min, but dropped to 16 ± 8 AU/min (P < 0.02; n = 7) 10 min after flow was stopped. Flow did not increase NO in tubules from mice lacking NO synthase 3 (NOS 3). Flow stimulated NO production by the same extent in tubules perfused with ion-free solution and physiological saline (20 ± 7 vs. 24 ± 6 AU/min; n = 7). Increasing stretch while reducing shear stress and pressure lowered NO generation from 42 ± 9 to 17 ± 6 AU/min (P < 0.03; n = 6). In the absence of shear stress, increasing pressure and stretch had no effect on NO production (2 ± 8 vs. 8 ± 8 AU/min; n = 6). Similar results were obtained in the presence of tempol (100 μmol/l), a O(2)(-) scavenger. Primary cultures of thick ascending limb cells subjected to shear stresses of 0.02 and 0.55 dyne/cm(2) produced NO at rates of 55 ± 10 and 315 ± 93 AU/s, respectively (P < 0.002; n = 7). Pretreatment with the NOS inhibitor l-NAME (5 mmol/l) blocked the shear stress-induced increase in NO production. We concluded that shear stress rather than pressure, stretch, or ion delivery mediates flow-induced stimulation of NO by NOS 3 in thick ascending limbs. |
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Authors:
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Pablo D Cabral; Nancy J Hong; Jeffrey L Garvin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-08-18 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 299 ISSN: 1522-1466 ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F1185-92 Citation Subset: IM |
Affiliation:
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Hypertension and Vascular Research Div., Dept. of Internal Medicine, Henry Ford Hospital, 2799 West Grand Blvd., Detroit, MI 48202, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Size Collagenases / chemistry, pharmacology Cyclic N-Oxides / pharmacology Enzyme Inhibitors / pharmacology Free Radical Scavengers / pharmacology Kidney Tubules / metabolism Loop of Henle / enzymology, metabolism*, physiology* Male Mice Mice, Inbred C57BL Mice, Knockout NG-Nitroarginine Methyl Ester / pharmacology Nitric Oxide / biosynthesis* Nitric Oxide Synthase Type III / antagonists & inhibitors, biosynthesis, genetics, metabolism Pressure Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Sodium Chloride / metabolism Spin Labels Stress, Mechanical* |
| Grant Support | |
ID/Acronym/Agency:
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HL-028982/HL/NHLBI NIH HHS; HL-070985/HL/NHLBI NIH HHS; HL-090550/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclic N-Oxides; 0/Enzyme Inhibitors; 0/Free Radical Scavengers; 0/Reactive Oxygen Species; 0/Spin Labels; 10102-43-9/Nitric Oxide; 2226-96-2/tempol; 50903-99-6/NG-Nitroarginine Methyl Ester; 7647-14-5/Sodium Chloride; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 1.14.13.39/Nos3 protein, rat; EC 3.4.24.-/Collagenases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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