Grants and Contributions:

Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023)

The renin-angiotensin system is activated at the time of birth in all mammalian species. In adult animals, the renin-angiotensin system is a key player in blood pressure regulation and the baroreflex control of the circulation. The role(s) for this hormonal system in blood pressure regulation and the baroreflex at the time of birth and in the newborn period is not known.
The short-term objective of our research is to obtain new knowledge regarding the role of the renin-angiotensin in the brain in regulating the newborn circulation. The long-term objective of our research is to further our understanding of blood pressure regulation during ontogeny and the role that the renin-angiotensin system plays during mammalian development. This follows logically from research we have been conducting for the last two decades and the advancements we have made in understanding reflexes in developing mammals.
In the proposed research, using in vivo approaches in conscious sheep at different stages of postnatal maturation, we will measure responses to different components of the renin-angiotensin system in the brain using specially designed cannula that we have developed and tested already. Our proposed research is hypothesis driven and will include direct measurements of the arterial baroreflex before and after central administration of renin-angiotensin system peptides and selective antagonists. In the developing sheep brain, the distribution of renin-angiotensin system components will also be assessed.
An understanding of the renin-angiotensin system of the developing brain in sheep, our short-term goal, as well as increasing knowledge of factors regulating the circulation in developing animals, our long-term goal, will have several impacts. First, it will provide new knowledge about brain physiology, the primary aim of a discovery grant. Second, our work is directly relevant to the field of veterinary medicine for both animal health and disease. This is because alterations in the baroreflex can lead to abnormal blood pressure control which can have dire consequences for the animal, if untreated. After we have evaluated the developmental profile of ATRs in the ovine brain, and depending upon the outcome of our research, future areas of inquiry may focus on specific lesions and/or injection sites within the CNS in order to reveal localized regions that may be regulating cardiovascular homeostasis and the baroreflex control of the circulation early in life.
Data obtained from the proposed research will provide new information regarding the brain renin-angiotensin system. Specifically, the role of brain renin-angiotensin II peptides in regulating resting cardiovascular homeostasis as well as the reflex control of the circulation during development. This research will provide a scientific basis for helping us to understand why the renin-angiotensin system is elevated at birth in all mammalian species.