Paton's group seeks to understand what changes within the central nervous system during the aetiology of neurogenic hypertension. Sympathetic nerve activity destined for the heart and arterioles is elevated prior to the onset of hypertension, which is suggestive of a causative role. In hypertension, cerebral vascular resistance is elevated causing brain hypoperfusion - a well known stimulant of sympathetic activity and hypertension. The microvasculature of the brainstem is also inflamed.
The hypothesis of elevated brainstem vascular resistance and inflammation as causative to hypertension is being explored in animal models and human patients. Transcriptomic analysis of brainstem genes altered in hypertension has led to exciting novel targets that are being validated with virally mediated transgenesis, stem cell transplantation, optogenetics and radio-telemetry in vivo.
The group's interest in mechanisms of central respiratory pattern generation has led to the observation that its modulation of sympathetic outflow is enhanced in hypertension. Additionally, data has shed light on plausible reasons for respiratory arrhythmias such as: sudden infant death and Rett syndromes. Data are being used to make mathematical models to assist in the further understanding of brainstem function as well as contributing to the Human Physiome project. A number of clinical translational studies driven by hypotheses gleaned from basic animal research are now underway in hypertensive patients.
2009: In collaboration with Dr Andrew Allen (Melbourne University) and Dr Anthony Pickering, we discovered that enhanced sympathetic activity precedes the onset of hypertension and is dependent on exacerbated modulation by the brainstem respiratory pattern generator.