Journal article
Spreading vasodilatation in the murine microcirculation: Attenuation by oxidative stress-induced change in electromechanical coupling
Journal of Physiology, Vol.591(8), pp.2157-2173
2013
Abstract
Regulation of blood flow in microcirculatory networks depends on spread of local vasodilatation to encompass upstream arteries; a process mediated by endothelial conduction of hyperpolarization. Given that endothelial coupling is reduced in hypertension, we used hypertensive Cx40ko mice, in which endothelial coupling is attenuated, to investigate the contribution of the renin-angiotensin system and reduced endothelial cell coupling to conducted vasodilatation of cremaster arterioles in vivo. When the endothelium was disrupted by light dye treatment, conducted vasodilatation, following ionophoresis of acetylcholine, was abolished beyond the site of endothelial damage. In the absence of Cx40, sparse immunohistochemical staining was found for Cx37 in the endothelium, and endothelial, myoendothelial and smooth muscle gap junctions were identified by electron microscopy. Hyperpolarization decayed more rapidly in arterioles from Cx40ko than wild-type mice. This was accompanied by a shift in the threshold potential defining the linear relationship between voltage and diameter, increased T-type calcium channel expression and increased contribution of T-type (3μmoll-1 NNC 55-0396), relative to L-type (1μmoll-1 nifedipine), channels to vascular tone. The change in electromechanical coupling was reversed by inhibition of the renin-angiotensin system (candesartan, 1.0mgkg-1day-1 for 2weeks) or by acute treatment with the superoxide scavenger tempol (1mmoll-1). Candesartan and tempol treatments also significantly improved conducted vasodilatation. We conclude that conducted vasodilatation in Cx40ko mice requires the endothelium, and attenuation results from both a reduction in endothelial coupling and an angiotensinII-induced increase in oxidative stress. We suggest that during cardiovascular disease, the ability of microvascular networks to maintain tissue integrity may be compromised due to oxidative stress-induced changes in electromechanical coupling. © 2013 The Physiological Society.
Details
- Title
- Spreading vasodilatation in the murine microcirculation: Attenuation by oxidative stress-induced change in electromechanical coupling
- Authors
- L Howitt (Author) - Australian National UniversityD J Chaston (Author) - Australian National UniversityShaun L Sandow (Author) - University of New South WalesK I Matthaei (Author) - Australian National UniversityF R Edwards (Author) - Australian National UniversityC E Hill (Author) - Australian National University
- Publication details
- Journal of Physiology, Vol.591(8), pp.2157-2173
- Publisher
- Wiley-Blackwell Publishing Ltd.
- Date published
- 2013
- DOI
- 10.1113/jphysiol.2013.250928
- ISSN
- 0022-3751; 0022-3751
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99448817002621
- Output Type
- Journal article
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