A high-salt diet in Dahl SS rats led to a significant selective impairment in sympathetic gain and elevated sympathetic tone, whereas consomic SS.13BN rats were protected from this impairment.
Mathematical modeling associates chromosome 13 with protection against high-salt diet-induced baroreflex impairment and elevated sympathetic tone in Dahl SS rats.
Salt-sensitive hypertension is known to be associated with dysfunction of the baroreflex control system in the Dahl salt-sensitive (SS) rat. However, neither the physiological mechanisms nor the genomic regions underlying the baroreflex dysfunction seen in this rat model are definitively known. Here, we have adopted a mathematical modeling approach to investigate the physiological and genetic origins of baroreflex dysfunction in the Dahl SS rat. We have developed a computational model of the overall baroreflex heart rate control system based on known physiological mechanisms to analyze telemetry-based blood pressure and heart rate data from two genetic strains of rat, the SS and consomic SS.13(BN), on low- and high-salt diets. With this approach, physiological parameters are estimated, unmeasured physiological variables related to the baroreflex control system are predicted, and differences in these quantities between the two strains of rat on low- and high-salt diets are detected. Specific findings include: a significant selective impairment in sympathetic gain with high-salt diet in SS rats and a protection from this impairment in SS.13(BN) rats, elevated sympathetic and parasympathetic offsets with high-salt diet in both strains, and an elevated sympathetic tone with high-salt diet in SS but not SS.13(BN) rats. In conclusion, we have associated several important physiological parameters of the baroreflex control system with chromosome 13 and have begun to identify possible physiological mechanisms underlying baroreflex impairment and hypertension in the Dahl SS rat that may be further explored in future experimental and modeling-based investigation.
Bugenhagen et al. (Wed,) conducted a other in Salt-sensitive hypertension (n=15). High-salt diet vs. Low-salt diet (0.4% NaCl) was evaluated on Sympathetic gain and tone. A high-salt diet in Dahl SS rats led to a significant selective impairment in sympathetic gain and elevated sympathetic tone, whereas consomic SS.13BN rats were protected from this impairment.
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