Abstract P186: Specific Knockout of Sox6 in Renin Expressing Cells Cause a Decrease in Renin Expression and Changes to Vascular Reactivity

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Introduction: Sox6 is a transcription factor known to be important for specification of different cell lineages, and important during embryonic development in vertebrates. Our group recently found that Sox6 plays a new function in renin expression control. Renin is an enzyme that controls the rate limiting step in the Renin Angiotensin Aldosterone System, a key regulator of blood pressure and thus hypertension. Here we report new findings in a novel transgenic mouse in which Sox6 is specifically knocked out in Renin expressing cells (Ren1d Cre /Sox6 fl/fl -Sox6 KO). Methods: Sox6 KO was used to determine the impact of Sox6 ablation in renin expressing cells on renin expression. Blood pressure and heart rate variability were measured by telemetry. Vascular reactivity was measured by wire myography and sympathetic nervous system renal input was determined by renal catecholamines assay. Results: We found that the specific Sox6 ablation in renin expressing cells produced a significant decrease in renin expression at a protein (40% fold decrease, n=7, P=0.01) and mRNA level (37 % fold decrease, n=4, P=0.01) compared to wild type mice. Our data indicates that Sox6 KO has no significant change in baseline blood pressure. However, there is a decrease in heart rate variability in Sox6 KO mice compared to wild type, indicating a dysregulation in the sympathetic and parasympathetic nervous systems (3.22±0.19 vs 1.14±0.32 LF/HF, n=10-13, P<0.05). Regarding vascular function, Sox6 KO mice have an enhanced sensitivity to vasodilators compared to wild type mice which may compensate for the decrease in renin expression (difference in response to sodium nitroprusside was found between 3 nM and 30 nM, n=3-11, P<0.05) and no difference in Acetylcholine response at any concentration. Furthermore, preliminary data indicates that there are no detectable differences in renal norepinephrine concentration between Sox6 KO and wild type mice. Conclusion: Our data indicate that Sox6 has a new function in renin-expressing cells that modulate blood pressure, heart rate variability, and vascular reactivity. Currently we are studying changes in the expression of vascular tone genes in endothelial and smooth muscle cells and changes in the sympathetic tone in the kidney and vascular system.