1: Cardiovasc Res. 2008 Aug 1;79(3):527-36. Epub 2008 Mar 18.

Control of blood pressure variability in caveolin-1-deficient mice: role of
nitric oxide identified in vivo through spectral analysis.

Desjardins F, Lobysheva I, Pelat M, Gallez B, Feron O, Dessy C, Balligand JL.

Unit of Pharmacology and Therapeutics, Université catholique de Louvain, UCL-FATH
5349, Vésale+5, 52 Avenue Mounier, 1200 Brussels, Belgium.

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.


PMID: 18349137 [PubMed - in process]

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