Dr Lauren Howitt, Blood Vessel Group, Department of Neuroscience, JCSMR, ANU.
Hypertension is the major risk factor for cardiovascular disease, which itself is the leading cause of premature death worldwide. Hypertension is characterised by endothelial dysfunction and reduced nitric oxide (NO) bioavailability. However, some 30% of hypertensive patients exhibit a therapy resistant form which does not respond to current clinical treatments. We hypothesised that this is due to changes in the calcium channels mediating vascular tone. Patients suffering from severe vascular constriction called vasospasm, after subarachnoid haemorrhage, also fail to respond to treatment with serious mortality consequences. Identification of novel therapeutic targets for these conditions is therefore a high priority. Our experiments show that T-type calcium channels contribute minimally to tone under physiological conditions in vivo, however chronic reduction in NO bioavailability, as occurs during cardiovascular disease, significantly increases T-type channel function and this is reversible by inhibition of ROS.Dr