Guto Montezano Ashley Mutchler Lale Ertuglu, MD Hypertension Currently, the only way to diagnose salt-sensitivity is through diet protocols - now feasible! This is not chronic blood pressure development secondary to chronic perturbations. Normotensive people with normal kidneys can have salt-sensitivity #HYPHIP Hypertension Guto Montezano

Guto Montezano Ashley Mutchler Lale Ertuglu, MD Hypertension Absolutely - not yet studies but our ongoing studies indicate that autoimmunity impacts salt-sensitivity as well as insulin resistance #HYPHIP Hypertension

Q9 Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Lale Ertuglu, MD Could you please explain to us your methodology of salt-loading and depletion? And also, how did you select the participants of your study? #HYPHIP Hypertension

Guto Montezano Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Hypertension A9 3/3 We excluded patients who were on medications that modulate the immune system or blood pressure. For patients on anti-hypertensive medications, all antihypertensives were discontinued for at least 2 weeks before the study. Hypertension #HYPHIP

Q 11 Are there any gender differences in salt-sensitivity? Differences in response to salt loading? #HYPHIP Guto Montezano Hypertension Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Ashley Mutchler

Migdalia Buchan Francisco Rios Ashley Mutchler Lale Ertuglu, MD Hypertension Guto Montezano To clarify, in our paper we think EETs regulating APC ENaC are coming from the kidney. Not sure what specific cell type in the kidney but endothelial cells could be a source #HYPHIP Hypertension

Tanja Dudenbostel, MD, FASH, FAHA Guto Montezano Hypertension Ashley Mutchler We are not yet powered to answer this for immune mechanisms - it is ongoing but all large clinical trials that have rigorously phenotyped salt-sensitivity find it mainly in women

Tanja Dudenbostel, MD, FASH, FAHA Guto Montezano Hypertension Ashley Mutchler More in women even in pre-menopause but amplified by menopause

Q13 Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Lale Ertuglu, MD You have seen an association between IsoLv activation of APCs and pro-inflammatory cytokines in salt-sensitivity. Are these changes are associated with changes in vascular function or structure in your cohort? #HYPHIP Hypertension

Guto Montezano Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Hypertension A13 1/2 This is a great question. Dr. Laffer and colleagues previously showed that salt sensitivity is associated with increased vascular resistance, suggesting that vascular dysfunction plays a key role in salt sensitivity. Hypertension #HYPHIP

Guto Montezano Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Hypertension A13 2/2 While we could not assess vascular function in the current study, previously Meena Madhur David G Harrison found that T-cell activation and IL-17A production lead to vascular dysfunction by altering vascular reactivity and increasing vascular superoxide Hypertension #HYPHIP

Guto Montezano Ashley Mutchler Lale Ertuglu, MD Hypertension A14 salt-sensitive people have super sensitive and high expression of SGK1. Our data indicates not through the MR. It’s the GR. Aldo does not correlate with salt-sensitive hypertension #HYPHIP Hypertension

Lale Ertuglu, MD Guto Montezano Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Hypertension Meena Madhur David G Harrison Did see differences in pulse pressure as a crude estimate of arterial stiffness? #hyphip Guto Montezano Hypertension Lale Ertuglu, MD Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A.

Tanja Dudenbostel, MD, FASH, FAHA Guto Montezano Ashley Mutchler Lale Ertuglu, MD Hypertension These APCs express little to no MR unfortunately 😊

Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Guto Montezano Ashley Mutchler Hypertension In our previous study using CITE-sequence analysis, we found no significant change in the expression of any RAAS-related gene in APCs after salt loading and depletion. Hypertension #HYPHIP Guto Montezano frontiersin.org/journals/physi…

Francisco Rios Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Ashley Mutchler Hypertension Guto Montezano A12 Yes both innate and adaptive immunity appear to play key roles! This is a very interesting point to look into in future studies! Francisco Rios Hypertension #HYPHIP

Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Lale Ertuglu, MD it was amazing having you here with us today and congrats on your paper. I am looking forward to more from you all and get to see all your salt studies and other ones as well! A heartfelt thank you and I hope you enjoyed the chat! #HYPHIP

Tanja Dudenbostel, MD, FASH, FAHA Guto Montezano Ashley Mutchler Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. Hypertension Meena Madhur David G Harrison We did not see a difference in baseline pulse pressure between salt-sensitivity tertiles, but pulse pressure significantly decreased from salt-loading to depletion in salt-sensitive people compared to salt-resistant Hypertension #HYPHIP

Guto Montezano Francisco Rios Ashley Mutchler Lale Ertuglu, MD Q12 - in our initial paper published in jci we performed a comprehensive analysis and found IsoLgs as extremely potent compared to other lipid mediators #HYPHIP Hypertension

Our summer research med student Treiy Tinich presenting his amazing work as part of the Vanderbilt Diabetes Center summer research and training program! Annet Kirabo D.V.M., M.Sc., Ph.D., F.A.H.A. #KiraboLab #NIDDK