- Biomedical Sciences Graduate Program Director 2017 - 2020
- Signature Program in Cardiovascular and Metabolic Disease Leader 2008 - 2017
My primary research interests are vascular physiology, hypertension and blood pressure control. My current research focuses on altered signal transduction in vascular cells during the development and maintenance of hypertension. This involves studies in vascular smooth muscle cells, endothelial cells and arterial segments. The long-term goal of these investigations is elucidation of the mechanisms responsible for elevated vascular contractility in hypertension and the development of pharmacological tools to reverse this hypersensitivity.
A major emphasis is investigating vascular effects of sleep apnea. We have developed a rat model of sleep apnea by exposing animals to intermittent hypoxia during their sleep period. Using this model, we have determined that the vasoactive peptide endothelin appears to initiate sustained hypertension (Kanagy et al 2001). We have also determined that 14 days of intermittent hypoxia initiates profound vascular changes that alter both endothelial function and vascular smooth muscle cell responses to endothelin. Ongoing studies are investigating the role of reactive oxygen species in these changes and deciphering the molecular mechanisms leading to augmented vasoconstriction to the endogenous peptide, endothelin.
A second ongoing project is investigating the cardiovascular effects of the environmental pollutant, diesel exhaust. We have found that even a short exposure to diesel exhaust causes profound alterations in coronary artery function and that repeated exposures initiate systemic alterations in both cardiac and vascular function.
We have recently been studying the contribution of hydrogen sulfide to the control of blood pressure and blood flow. These studies are exploring the site of synthesis of hydrogen sulfide, the mechanism of action in the vascular wall and the effect of intermittent hypoxia on the pathway.