Endothelin Modulates Rhythm Disturbances and Autonomic Responses to Acute Emotional Stress in Rats

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

All corrections should be done before the start of publication process

There is no highlights ---should be

There are a huge number of abbreviations--it will be better if you create a separate table for this.

Abstract should be improved and contained backgrounds including aims , Methods , Results and Conclusion

There is no recommendations ?

From LN/14-22---no need for simple summary or considered part of the conclusion and should directed to the end of the paper  , before the reference lists

LN/25--pressor or pressure ???

LN/25--arrhythmogenesis----more details are requested

LN/29--rats--what is the difference between the two strains , gender, size and weight beside numbers all should cited

LN/35--blunt autonomic response---what is the mechanism ?

LN/36---explain the pathogenesis

LN/36--add we can concluded that---not our findings

Endothelin as a powerful vasoconstrictors had a big role in the beginning of the inflammatory responses ---explain its role and relation with emotion crises ??

LN/43---add reference

LN/44--Walter Cannon--who is this !!!!!and cite as reference---name year

LN/47/LN/49---add reference for this

LN/42---till LN/49--just one reference --not enough

LN/51---add node not mode

LN/53---fight or flight--explain for ordinary readers

LN/51--what about bundle of Hiss and Purkinje fiber also have a role or not ???

LN/54-55---more explanations are needed

From LN/57-64---delete it (just history)

From LN/88-96--delete

From LN/103-110---no need

Introduction is very long --why ??? be more summarize and at the end clear the aims of the study well

LN/113---start as A total number of------and delete the experiment

LN/127---add experimental design instead of the others

LN/145--neuroendocrine and CV responses---how ???

LN/204--there is no reference for the statistical analysis --why ?

What about the clinical signs that observed during running this investigation ?

What about the characteristic postmortem lesions (heart, brain , kidneys--etc )???

What about the recorded percentage of mortalities ??

What about the pathological-score -lesions for comparison of the different groups ??

Why the authors did not do a histological sections for more confirmation ??

Write as Table (1):--------------/Fig.(1):----------etc--apply for all

Results should be more concise and summarize

All data under tables or figures should be more summarize

Discussion is very long --why ???should be based on debating the obtained results with those of the previous investigators results

As volume/issue/number/pages---all are available--so no need for the link(s)---apply for all

Some cited references need to be more update

Some cited references are contained more than 6 authors --why ?? should be 6 at the maximum plus etal with the last ones --apply for all(for example---ref--18,19,22,--etc)

What a huge number of references were used (67)--why ?

There is no map for the study area??

There is no gross figures for the feared rats or heart???

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The manuscript by Mouchtouri et al., aims to elucidate the pathophysiological role of ET-1, using a model of acute emotional stress established in conscious rats. The results obtained allow them to conclude that chronically elevated plasma endothelin levels inhibit autonomic responses to acute emotional stress, resulting in vagal dominance and bradyarrhythmias. According to the authors, these results provide further information on the pathophysiology of stress-induced tachyarrhythmias and syncope. The experimental model is widely used by the group, which supports its expertise on the subject. The work is very interesting and well developed, reaching valid conclusions. There are only two aspects that I would like the authors to review in the manuscript:

- There are works that suggest some differences with what was obtained by the authors. “It has been shown that ETB-deficient rats have elevated global sympathetic tone”, or that “endothelin 1 stimulates the sympathetic nervous system by activating the subtype A receptor”. These differences should be discussed by the authors in the discussion.

- The legends of the figures should be more explanatory, headed by a title and the number of animals used in each experimental group.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 3 Report

Comments and Suggestions for Authors

This study found that acute emotional stress (AES) caused increased sympathetic stimulation and vagal withdrawal in wild-type rats, and in ET_B-deficient rats there was blunted sympathetic stimulation and bradyarrhythmia.

 

 

This study did not measure endothelin-1 levels in rats directly, so there is no convincing evidence that the blunted sympathies and bradyarrhythmias in ET_B-deficient rats are caused by high levels of ET-1. 

 

How endothein-1 (ET-1) affects catecholamines (epinephrine and norepinephrine) needs to be discussed. Because the sympathetic nerves innervate the heart through the production of catecholamines to stimulate heart cells.

 

The intervention was given to rats in the morning while these rats are nocturnal animals. As we know that autonomic activity is influenced by the biological rhythms. What is the reason for the intervention to be carried out in the morning

 

 

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf