The cardiac-sympathetic contribution to blood pressure regulation

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The arterial baroreflex is arguably one of the most important reflexes in the control of arterial blood pressure (BP). The baroreflex buffers acute fluctuations in BP that occur during physiological stressors by controlling cardiac output and total peripheral resistance. Thus the `output' from the baroreflex is considered to consist of a heart rate (cardiopulmonary arm) and vascular component (sympathetic arm). In conducting integrative physiological studies in rodents with spinal transection over the last 5-8 years, my lab has made a number of key observations that imply there may also be a cardiac inotropic (i.e., cardiac-sympathetic) arm to the arterial baroroeflex. Recently, we have found that when the arterial baroreceptors are unloaded there is not only an increase in peripheral vascular resistance and heart rate but there is also an increase in cardiac inotropic function. Though such a response is logical, direct evidence supporting the presence of a cardiac-inotropic arm to the arterial baroreflex control of blood pressure is lacking. Moreover, fundamental shortcomings exist in our understanding of the neuroanatomical pathways that are important in transducing this response from the brainstem to the heart and blood vessels. Over the next 5 years we will comprehensively study the presence of a functional cardiac-inotropic arm to the baroreflex along with the underlying neuroanatomic pathways that control this response, with a particular emphasis on spinal segmental control. We will specifically assess whether mechanical and pharmacological manipulation of the baroreflex results in similar cardiac and vascular outputs, as well as testing whether control mechanisms differ by sex and are impacted by activation of the chemoreflex. We will also continue our ongoing efforts to modify the post-processing software available for human sympathetic recordings to study and decode sympathetic neural transmission in rodents, wherein we will additionally relate such strategies to end-organ function. Establishing and validating the presence of a functional cardiac-inotropic arm to the baroreflex and determining the underlying neuroanatomical control is expected to advance our basic understanding of how the baroreflex functions to maintain arterial blood pressure. The studies proposed span a number of diverse fields and provide an excellent training environment for HQP who will be trained in all aspects of the surgical preparation and advanced data processing.