Document Detail


Control of blood pressure variability in caveolin-1-deficient mice: role of nitric oxide identified in vivo through spectral analysis.
MedLine Citation:
PMID:  18349137     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: In endothelial cells, caveolin-1 (cav-1) is known to negatively modulate the activation of endothelial nitric oxide synthase, a key regulator of blood pressure (BP). However, the impact of genetic alteration of cav-1 on vascular nitric oxide (NO) production and BP homeostasis in vivo is unknown. METHODS AND RESULTS: We used spectral analysis of systolic blood pressure (SBP) variability in mice chronically equipped with telemetry implants to identify frequency ranges (0.05-0.4 Hz; very low frequency, VLF) specifically responding to NO, independently of changes in absolute BP or systemic neurohormone levels. VLF variability was inversely correlated to aortic vasodilator-stimulated Ser(239) phosphoprotein (VASP) phosphorylation, reflecting NO bioactivity. We show that mice deficient in cav-1 have decreased VLF variability paralleled with enhanced systemic and vascular production of NO at unchanged mean SBP levels. Conversely, VLF variability was increased upon acute injection of mice, with a peptide containing the caveolin-scaffolding domain (CSD; residues 82-101) fused to an internalization sequence of antennapedia that decreased vascular and circulating NO in vivo. CONCLUSION: These data highlight the functional importance of cav-1 for the production of bioactive NO in conduit arteries and its control of central BP variability. Given the impact of the latter on target organ damage, this raises the interest for genetic, pharmacological, or molecular interventions that modulate cav-1 expression in diseases with NO-dependent endothelial dysfunction.
Authors:
Fanny Desjardins; Irina Lobysheva; Michel Pelat; Bernard Gallez; Olivier Feron; Chantal Dessy; Jean-Luc Balligand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-03-18
Journal Detail:
Title:  Cardiovascular research     Volume:  79     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-30     Completed Date:  2008-12-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  527-36     Citation Subset:  IM    
Affiliation:
Unit of Pharmacology and Therapeutics, Université catholique de Louvain, UCL-FATH 5349, Vésale+5, 52 Avenue Mounier, 1200 Brussels, Belgium.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aorta / metabolism
Blood Pressure* / drug effects,  genetics
Blood Pressure Monitoring, Ambulatory / methods*
Cattle
Caveolin 1 / deficiency,  genetics,  metabolism*
Cells, Cultured
Circadian Rhythm*
Dose-Response Relationship, Drug
Electrocardiography, Ambulatory
Electron Spin Resonance Spectroscopy
Endothelial Cells / drug effects,  enzymology,  metabolism*
Enzyme Inhibitors / pharmacology
Fourier Analysis*
Heart Rate
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / blood*
Nitric Oxide Donors / pharmacology
Nitric Oxide Synthase Type II / antagonists & inhibitors,  metabolism
Nitric Oxide Synthase Type III
Nitroprusside / pharmacology
Peptide Fragments / pharmacology
Signal Processing, Computer-Assisted
Telemetry*
Chemical
Reg. No./Substance:
0/Cav1 protein, mouse; 0/Caveolin 1; 0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 0/Peptide Fragments; 10102-43-9/Nitric Oxide; 15078-28-1/Nitroprusside; 50903-99-6/NG-Nitroarginine Methyl Ester; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse

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