Blood pressure and flow are fundamental to cell/ tissue survival. A primary determinant of blood pressure is the resistance to blood flow offered by the small pre-capillary arteries termed "resistance arteries".  A number of disease conditions including hypertension and diabetes are associated with resistance artery dysfunction.  This project will focus on the influence of reactive oxygen species (ROS) derived from the adventitial layer of resistance arteries and how this influences underlying vascular smooth muscle cell tone and endothelial relaxing factors. The project will ultimately aim to increase our understanding of the cellular mechanism driving vascular function and in particular how mechanisms of resistance artery tone are influenced via intravascular wall cell to cell communication. This study of the influence of reactive oxygen species and diabetes in vascular auto-regulation of total peripheral vascular resistance has not been studied. This work has great potential to identify novel signalling interactions and focused therapeutic targets.

We have significant clinical collaboration in this area of our work and human diseased and healthy tissues will be available to the project.

Project Aim: Elucidation of the role of ROS as an essential cell signalling factor in the generation of pressure-dependent vascular contraction in health and diabetes.

Techniques to be used: Laboratory based methods employed include small artery myography, cell and tissue culture. Cell transfection with siRNA, western blotting, QC-PCR, ELISA coupled with histology, immunohistochemistry and light and fluorescent microscopy.

1.       Myogenic, mechanical and structural characteristics of resistance arterioles from healthy and ischaemic subjects. Coats P. Clin Sci (Lond). 2003; 105: 683-9.

2.       Adventitia-derived hydrogen peroxide impairs relaxation of the rat carotid artery via smooth muscle cell p38 mitogen-activated protein kinase. Cascino T, Csanyi G, Al Ghouleh I, Montezano AC, Touyz RM, Haurani MJ, Pagano PJ. Antioxid Redox Signal. 2011; 15: 1507-15

3.       Zainalabidin S, Wadsworth RM, Coats P. Adventitial ablation technique that permits the assessment of adventitial-dependent contribution to microvascular contractile function. Anal Biochem. 2016; 499: 71-7