Sympathetic Axonal Activity in Conscious Rats During Development of Hypertension

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DESCRIPTION (provided by applicant): Sympathetic nerve activity (SNA) has been recorded in conscious humans and animals for more than 3 decades with the intent of determining whether elevated SNA contributes to the development of heart disease and hypertension. Although the procedure has become relatively common, (1) the duration of the recordings and (2) the interpretation of multiunit activity of functionally diverse neurons remain problematic. Our laboratory and a few others have now performed long term SNA recording (weeks) in conscious animals allowing the examination of SNA during the development of cardiovascular disease. The second problem has been addressed in conscious humans and anesthetized animals using percutaneous high impedence electrodes and nerve dissection, respectively. Unfortunately, neither approach allows for long term recording of individual axons. This proposal is designed to develop procedures for recording single unit SNA in conscious rats during the development of hypertension. We have been able to record from single axons in the renal, adrenal and lumbar nerves for more than two weeks in conscious rats. This proposal will develop techniques for isolating and characterizing single axons that can be recorded for prolonged periods (days to weeks). Finally, this approach will be used to directly examine the activity of single characterized sympathetic neurons during the development of DOCA/salt hypertension. We will determine in single axons whether the early phases of mineralocorticoid hypertension are associated with greater resting or evoked sympathetic nerve activity. Moreover, we will directly examine whether the elevated SNA is due to individual neurons firing more often or whether more neurons are recruited during the development of experimental hypertension. PUBLIC HEALTH RELEVANCE: Many studies have suggested that hypertension and heart disease may be caused by increased sympathetic nerve activity. This project is designed to develop a method for directly testing this hypothesis by recording from single sympathetic nerves during the development of hypertension. This procedure could provide a novel and direct method for proving the role of the sympathetic nervous system in cardiovascular disease.