| Mechanisms of carbon monoxide attenuation of tubuloglomerular feedback. | |
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MedLine Citation:
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PMID: 22508834 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Carbon monoxide (CO) is a physiological messenger with diverse functions in the kidney, including controlling afferent arteriole tone both directly and via tubuloglomerular feedback (TGF). We have reported that CO attenuates TGF, but the mechanisms underlying this effect remain unknown. We hypothesized that CO, acting via cGMP, cGMP-dependent protein kinase, and cGMP-stimulated phosphodiesterase 2, reduces cAMP in the macula densa, leading to TGF attenuation. In vitro, microdissected rabbit afferent arterioles and their attached macula densa were simultaneously perfused. TGF was measured as the decrease in afferent arteriole diameter elicited by switching macula densa NaCl from 10 to 80 mmol/L. Adding a CO-releasing molecule (CORM-3, 5 × 10(-5) mol/L) to the macula densa blunted TGF from 3.3 ± 0.3 to 2.0 ± 0.3 μm (P<0.001). The guanylate cyclase inhibitor LY-83583 (10(-6) mol/L) enhanced TGF (5.8 ± 0.6 μm; P<0.001 versus control) and prevented the effect of CORM-3 on TGF (LY-83583+CORM-3, 5.5 ± 0.3 μm). Similarly, the cGMP-dependent protein kinase inhibitor KT-5823 (2 × 10(-6) mol/L) enhanced TGF and prevented the effect of CORM-3 on TGF (KT-5823, 6.0 ± 0.7 μm; KT-5823+CORM-3, 5.9 ± 0.8 μm). However, the phosphodiesterase 2 inhibitor BAY-60-7550 (10(-6) mol/L) did not prevent the effect of CORM-3 on TGF (BAY-60-7550, 4.07 ± 0.31 μm; BAY-60-7550+CORM-3, 1.84 ± 0.31 μm; P<0.001). Finally, the degradation-resistant cAMP analog dibutyryl-cAMP (10(-3) mol/L) prevented the attenuation of TGF by CORM-3 (dibutyryl-cAMP, 4.6 ± 0.5 μm; dibutyryl-cAMP+CORM-3, 5.0 ± 0.6 μm). We conclude that CO attenuates TGF by reducing cAMP via a cGMP-dependent pathway mediated by cGMP-dependent protein kinase rather than phosphodiesterase 2. Our results will lead to a better understanding of the mechanisms that control the renal microcirculation. |
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Authors:
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Yilin Ren; Martin A D'Ambrosio; Hong Wang; John R Falck; Edward L Peterson; Jeffrey L Garvin; Oscar A Carretero |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2012-04-16 |
Journal Detail:
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Title: Hypertension Volume: 59 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-05-17 Completed Date: 2012-07-25 Revised Date: 2012-12-25 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1139-44 Citation Subset: IM |
Affiliation:
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Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aminoquinolines
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pharmacology Animals Arterioles / drug effects, physiology Bucladesine / pharmacology Carbazoles / pharmacology Carbon Monoxide / metabolism, physiology* Cyclic AMP / metabolism Cyclic GMP / metabolism Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors, metabolism Cyclic Nucleotide Phosphodiesterases, Type 2 / antagonists & inhibitors, metabolism Enzyme Inhibitors / pharmacology Feedback, Physiological / drug effects, physiology* Guanylate Cyclase / antagonists & inhibitors, metabolism Imidazoles / pharmacology Kidney Glomerulus / metabolism, physiology* Kidney Tubules, Distal / blood supply, metabolism, physiology* Organometallic Compounds / metabolism, pharmacology Rabbits Triazines / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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GM-031278/GM/NIGMS NIH HHS; P01 HL-090550/HL/NHLBI NIH HHS; P01 HL090550/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/2-(3,4-dimethoxybenzyl)-7-(1-(1-hydroxyethyl)-4-phenylbutyl)-5-methylimidazo(5,1-f)(1,2,4)triazin-4 (3H)-one; 0/Aminoquinolines; 0/Carbazoles; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Organometallic Compounds; 0/Triazines; 0/tricarbonylchloro(glycinato)ruthenium(II); 126643-37-6/KT 5823; 362-74-3/Bucladesine; 60-92-4/Cyclic AMP; 630-08-0/Carbon Monoxide; 7665-99-8/Cyclic GMP; 91300-60-6/6-anilino-5,8-quinolinedione; EC 2.7.11.12/Cyclic GMP-Dependent Protein Kinases; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 2; EC 4.6.1.2/Guanylate Cyclase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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