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The Australian National University
The John Curtin School of Medical Research
ANU COLLEGE OF MEDICINE AND HEALTH SCIENCES

 

Blood Vessel Group - Research

The coordinated behaviour of small arteries is fundamental to the regulation of blood flow, blood pressure and adequate tissue perfusion. This coordination occurs because the cells which make up the blood vessel wall are electrically and chemically coupled through membrane channels called gap junctions. In hypertension and diabetes, homeostatic conditions are perturbed and excessive constriction of the muscle cells in the blood vessel wall reduces blood vessel diameter and blood flow to body organs. This imbalance often results from dysfunction of the endothelial lining, decreasing its ability to release molecules, like nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), which cause vasodilation. The aim of our studies has been to characterize cell coupling and its contribution to normal vascular function and to determine whether alterations to coupling are responsible for vascular abnormalities. Our past results have implicated cell coupling in the action of EDHF and established a link between nitric oxide and alterations in cell coupling in diabetes.
Over the past year we have continued to amass evidence that coupling amongst the cells in the vascular wall is pivotal to homeostasis. With our collaborators in Japan, we have found that cell coupling in the renal vasculature is essential to blood pressure control through regulation of the renin-angiotensin system. We have also identified in two different forms of hypertension, changes in common to three molecules, one of which is expected to lead to reductions in nitric oxide. Finally, we have found that upregulation of the enzyme responsible for the formation of nitric oxide is protective against induction of experimental diabetes.