Renin-a in the Subfornical Organ Plays a Critical Role in the Maintenance of Salt-Sensitive Hypertension
, Caleb J. Worker 1,2, Ariana Julia B. Gayban 1,2, Sophie Buller 3, Ryosuke Satou 4 and Yumei Feng Earley 1,2,*
Round 1
Reviewer 1 Report
In the manuscript by Cooper and colleagues, the authors investigated the hypothesis that renin-a produced locally in the brain contributes to the pathogenesis of hypertension using a DOCA-salt hypertension model. The overall conclusions of findings demonstrate that endogenous renin-a within the SFO is important for the pathogenesis of salt-sensitive hypertension. The experiments were conducted with proper controls, manuscript was well written, and the conclusions were well drawn. Below are few comments:
1. Figure 1. The total renin levels were detected in different brain regions at the end of the DOCA-salt hypertension paradigm suggest that the association of increased mRNA with hypertension. However, when this increase is happening and does this increase in mRNA correlates with the increase in blood pressure during the time-course of DOCA-salt treatment?
2. Figure 3. Figure 3C is missing.
3. Figure 5A. SFO targeted AAV2 injections were performed 1 week prior to DOCA-salt hypertension. When will be the highest/peak expression of target gene (or knockdown of target gene) is achieved? Does one week prior is sufficient? Figure 4 was shown after 4 weeks. Does injecting AAV2 2 weeks prior to DOCA-salt will influence the effect on blood pressure?
4. Figure 5C. The MAP was significantly different at the end of 21 days. However, please show the statistical difference at each day.
5. Figure 6. The dose of DOCA was used in the present study is high according to authors. Does DOCA dose will influence the outcome of the present study?
6. What is the contribution of Renin-a to the over all renin activity in the brain?
Author Response
We thank the reviewer for their constructive comments, which have helped to improve our manuscript. All questions and concerns are addressed in a point-by-point manner. Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Figure 3 should include an image of an entire brain slice with labeling in addition to the already shown higher zoom GFP image.
Figure 5B: it looks like there is significance between the blue and orange lines early in administration of NaCl
Figures using viral injections should include images of injection sites.
Figure 9c should include DOCA
Author Response
We thank the reviewer for their constructive comments, which have helped to improve our manuscript. All questions and concerns are addressed in a point-by-point manner. Please see the attachment.
Author Response File: Author Response.pdf
