The overall objective of this proposal is to evaluate a central neural mechanism involved in the long term regulation of cardiovascular function that may ultimately be involved in the pathogenesis of certain forms of hypertension. Selective disruption of central nervous system function can produce acute as well as chronic elevations in arterial blood pressure (AP) and influence cardiovascular reflexes. The rostra ventral lateral medulla (RVLM) is important for the maintenance of baseline AP and its reflexive regulation and is comprised of two neurochemically distinct neuronal cell populations, the C1 cell population that contains the enzyme phenylethanolamine-N-transferase (PNMT) and those cells that do not contain PNMT. Recently a technique has been developed to selectively destroy the C1 cell population in rats that has allowed the evaluation of the role of these neurons in cardiovascular regulation. The proposed studies will examine the effect of C1 RVLM lesions in two strains of genetically hypertensive rats (spontaneously hypertensive rats, SHR and Dahl salt-sensitive rats, DS) using radio telemetry to monitor AP and heart rate in freely moving rats prior to and during an extended time course following destruction of C1 neurons. Responses to stressful stimuli and anti-hypertensive drugs will also be tested. These experiments will test the hypothesis that C1-RVLM neurons are important for the maintenance of hypertension in these two models, extending acute studies in anesthetized rats suggesting that the RVLM is important in these forms of hypertension and further our understanding of how the central nervous system is involved in the pathogenesis of hypertension.
