| Neuronal nitric oxide synthase supports Renin release during sodium restriction through inhibition of phosphodiesterase 3. | |
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MedLine Citation:
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PMID: 20651700 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Mice with targeted deletion of neuronal nitric oxide (NO) synthase (nNOS⁻(/)⁻) display inability to increase plasma renin concentration (PRC) in response to sodium restriction. nNOS has a distinct expression at the macula densa (MD), and in the present study, it was tested whether nNOS supports renin release by cyclic guanosine monophosphate (cGMP)-mediated inhibition of cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase 3 (PDE3) in juxtaglomerular (JG) cells. METHODS: The experiments were performed in conscious nNOS⁻(/)⁻ and wild types after 10 days on a low-sodium diet by acute treatment with the PDE3-inhibitor milrinone, the PDE5 inhibitor zaprinast, or vehicle, using a crossover study protocol. PRC was measured with the antibody-trapping technique and blood pressure with telemetry. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were estimated by measurements of inulin- and para-amino hippuric acid (PAH) clearances, respectively. RESULTS: The basal PRC was reduced in nNOS⁻(/)⁻ compared to the wild types. Administration of milrinone caused a more pronounced PRC increase in nNOS⁻(/)⁻, resulting in normalized renin levels, whereas PDE5 inhibition did not affect PRC in any genotype. The blood pressure was similar in both genotypes, and milrinone did not affect blood pressure compared to vehicle. GFR and RPF were similar at baseline and were reduced by milrinone. CONCLUSIONS: The present study provides in vivo evidence supporting the view that NO, selectively derived from nNOS, mediates renin release during sodium restriction by inhibiting PDE3, which would increase renin release by elevating cAMP levels in the JG cells. |
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Authors:
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Johan Sällström; Boye L Jensen; Ole Skøtt; Xiang Gao; A Erik G Persson |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-22 |
Journal Detail:
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Title: American journal of hypertension Volume: 23 ISSN: 1941-7225 ISO Abbreviation: Am. J. Hypertens. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-19 Completed Date: 2011-01-31 Revised Date: 2011-06-30 |
Medline Journal Info:
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Nlm Unique ID: 8803676 Medline TA: Am J Hypertens Country: United States |
Other Details:
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Languages: eng Pagination: 1241-6 Citation Subset: IM |
Affiliation:
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Department of Medical Cell Biology, Uppsala University, Sweden. johan.sallstrom@mcb.uu.se |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects, physiology Cyclic AMP / metabolism Cyclic GMP / metabolism Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism* Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism Female Juxtaglomerular Apparatus / physiology Kidney Cortex / drug effects, enzymology Male Mice Mice, Inbred Strains Mice, Knockout Milrinone / pharmacology Nitric Oxide Synthase Type I / genetics*, metabolism* Phosphodiesterase 3 Inhibitors / pharmacology Phosphodiesterase 5 Inhibitors / pharmacology Purinones / pharmacology Renal Circulation / drug effects, physiology Renin / metabolism* Sodium Chloride, Dietary / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Phosphodiesterase 3 Inhibitors; 0/Phosphodiesterase 5 Inhibitors; 0/Purinones; 0/Sodium Chloride, Dietary; 37762-06-4/zaprinast; 60-92-4/Cyclic AMP; 7665-99-8/Cyclic GMP; 78415-72-2/Milrinone; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nos1 protein, mouse; EC 3.1.4.17/Cyclic Nucleotide Phosphodiesterases, Type 3; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5; EC 3.1.4.35/Pde5a protein, mouse; EC 3.4.23.15/Renin |
| Comments/Corrections | |
Comment In:
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Am J Hypertens. 2010 Nov;23(11):1157
[PMID:
20956962
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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