Physiology of Hypertension-David B. Averill, Ph.D.
The primary goal of my laboratory is to define the peripheral vascular, cardiac, and central neural mechanisms through which the renin angiotensin system contributes to the regulation of blood pressure. How these mechanisms are altered in the development and maintenance of high blood pressure is of particular interest. One component of my laboratory studies the hemodynamic mechanisms responsible for the cardiovascular actions of the renin angiotensin system. We have sought to define the receptors subtypes at which various angiotensin peptides affect blood pressure. In the course of trying to achieve this objective I have utilized a variety of preparations. These include instrumentation of rats for chronic telemetry measurement of blood pressure and heart rate, acute studies that focus on regional blood flow, and an in vitro preparation of isolated mesenteric blood vessels to assess vascular responsiveness to angiotensin peptides. The second component of my lab is the investigation of neural mechanisms involved in the regulation of blood pressure. The broad hypothesis underlying many of my studies is that angiotensin II acts at discrete sites in the caudal brainstem to shift the regulation of sympathetic nerve activity to higher blood pressures. Thus, I have sought to understand the central neural pathways at which angiotensin peptides alter sympathetic outflow and modulate baroreceptor reflex regulation of sympathetic nerve activity, heart rate, and blood pressure. To pharmacologically characterize the neurotransmitter systems affected by angiotensin II, selected brain sites are injected with peptides, peptide receptor antagonists, excitatory and inhibitory neurotransmitters, and neurotransmitter antagonists. To elucidate the neural pathways involved in control of cardiovascular actions of angiotensin II in the brain, we have combined neuronal tract tracing with immunocytochemistry for angiotensin peptides. A third component of my laboratory is a collaboration with Dr. Carlos Ferrario. Dr. Ferrario and I are interested in redefining the components of the renin angiotensin system in the heart with particular focus toward cardiac remodeling in hypertension and heart failure. A fourth component of my laboratory is the investigation of the central neural mechanisms responsible for hypertension that develops as a consequence of antenatal exposure to glucocorticoids. This project is being done in collaboration with Dr. James Rose of the Department of Obstetrics and Gynecology. Finally, the interaction between the renin angiotensin system and adipose tissue is a new research area in my laboratory. We are investigating the broad hypothesis that components of the renin angiotensin system contribute to the regulation of adipose tissue derived hormones as well as responsiveness of adipose tissue to insulin. These studies will be done in both the basic and clinical research setting.