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Role of dual-specificity protein phosphatase-5 in modulating the myogenic response in rat cerebral arteries. J Appl Physiol (1985) 2013 Jan 15;114(2):252-61

Date

11/23/2012

Pubmed ID

23172031

Pubmed Central ID

PMC3544499

DOI

10.1152/japplphysiol.01026.2011

Scopus ID

2-s2.0-84872285379   7 Citations

Abstract

The present study examined the role of the dual-specificity protein phosphatase-5 (DUSP-5) in the pressure-induced myogenic responses of organ-cultured cerebral arterial segments. In these studies, we initially compared freshly isolated and organ-cultured cerebral arterial segments with respect to responses to step increases in intravascular pressure, vasodilator and vasoconstrictor stimuli, activities of the large-conductance arterial Ca(2+)-activated K(+) (K(Ca)) single-channel current, and stable protein expression of DUSP-5 enzyme. The results demonstrate maintained pressure-dependent myogenic vasoconstriction, DUSP-5 protein expression, endothelium-dependent and -independent dilations, agonist-induced constriction, and unitary K(Ca) channel conductance in organ-cultured cerebral arterial segments similar to that in freshly isolated cerebral arteries. Furthermore, using a permeabilization transfection technique in organ-cultured cerebral arterial segments, gene-specific small interfering RNA (siRNA) induced knockdown of DUSP-5 mRNA and protein, which were associated with enhanced pressure-dependent cerebral arterial myogenic constriction and increased phosphorylation of PKC-╬▓II. In addition, siRNA knockdown of DUSP-5 reduced levels of phosphorylated ROCK and ERK1 with no change in the level of phosphorylated ERK2. Pharmacological inhibition of ERK1/2 phosphorylation significantly attenuated pressure-induced myogenic constriction in cerebral arteries. The findings within the present studies illustrate that DUSP-5, native in cerebral arterial muscle cells, appears to regulate signaling of pressure-dependent myogenic cerebral arterial constriction, which is crucial for the maintenance of constant cerebral blood flow to the brain.

Author List

Wickramasekera NT, Gebremedhin D, Carver KA, Vakeel P, Ramchandran R, Schuett A, Harder DR

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain
Cells, Cultured
Cerebral Arteries
Cerebrovascular Circulation
Dual-Specificity Phosphatases
Male
Models, Animal
Muscle Development
Muscle, Smooth, Vascular
Patch-Clamp Techniques
Potassium Channels, Calcium-Activated
RNA, Messenger
RNA, Small Interfering
Rats
Rats, Sprague-Dawley
Regional Blood Flow
Signal Transduction
Vasoconstriction
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d