Hypothermia Inhibits Dexmedetomidine-Induced Contractions in Isolated Rat Aortae
, Yeran Hwang 4,†, Kyeong-Eon Park 4, Sungil Bae 5, Seong-Ho Ok 1,2,3, Seung-Hyun Ahn 3,5, Gyujin Sim 3,5, Moonju Bae 5 and Ju-Tae Sohn 3,4,*
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe authors studied the effect of hypothermia on dexmedetomidine-induced contraction in endothelium-intact aortas with or without nitric oxide synthase inhibitor NW-nitro-L-arginine methyl ester and in endothelium-depleted aortas without or with Krebs solution without calcium. The results showed that hypothermia inhibits dexmedetomidine-induced contraction in the aorta with intact endothelium with L-NAME or in the aorta without endothelium; that hypothermia had almost no effect on dexmedetomidine-induced contraction in endothelium-free aorta with calcium-free Krebs solution, and that subsequent contraction induced by calcium addition was inhibited by hypothermia. These results suggested that hypothermia inhibited dexmedetomidine-induced contraction, which was mediated primarily by impeding calcium influx and partially by attenuating pathways involving PKC and Rho-kinase activation.
The study is well conducted, and the results are the beginning of new information.
The graphs are clear and the bibliography correct.
I suggest reviewing a few English errors probably due to typos.
Comments on the Quality of English Language
I suggest reviewing a few English errors probably due to typos.
Author Response
Response to Reviewer #1’s comments
Thank you very much for your valuable comments.
The authors studied the effect of hypothermia on dexmedetomidine-induced contraction in endothelium-intact aortas with or without nitric oxide synthase inhibitor NW-nitro-L-arginine methyl ester and in endothelium-depleted aortas without or with Krebs solution without calcium. The results showed that hypothermia inhibits dexmedetomidine-induced contraction in the aorta with intact endothelium with L-NAME or in the aorta without endothelium; that hypothermia had almost no effect on dexmedetomidine-induced contraction in endothelium-free aorta with calcium-free Krebs solution, and that subsequent contraction induced by calcium addition was inhibited by hypothermia. These results suggested that hypothermia inhibited dexmedetomidine-induced contraction, which was mediated primarily by impeding calcium influx and partially by attenuating pathways involving PKC and Rho-kinase activation.
The study is well conducted, and the results are the beginning of new information.
The graphs are clear and the bibliography correct.
I suggest reviewing a few English errors probably due to typos.
Response:
The English of this revised manuscript was reviewed by a native English speaker from Editage.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsThe author effectively elucidated how hypothermia hinders the contraction induced by dexmedetomidine in the isolated rat aorta. I have full confidence in the study.
I observed a similarity in another published article titled "Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration" in the Korean Journal of Anesthesiology (2012 Sep; 63(3): 253–259). Could you clarify the differences between these two papers?
Author Response
Response to Reviewer #2’s comments
Thank you very much for your valuable comments.
The author effectively elucidated how hypothermia hinders the contraction induced by dexmedetomidine in the isolated rat aorta. I have full confidence in the study.
I observed a similarity in another published article titled "Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration" in the Korean Journal of Anesthesiology (2012 Sep; 63(3): 253–259). Could you clarify the differences between these two papers?
Response:
Thank you very much.
The previous report entitled “Dexmedetomidine-induced contraction of isolated rat aorta is dependent on extracellular calcium concentration” examined the underlying mechanisms associated with dexmedetomidine-induced contraction in isolated endothelium-denuded rat aortae using only isometric tension measurement. However, our current study examined the effect of hypothermia on the contraction induced by dexmedetomidine in isolated endothelium-intact and -denuded rat aortae using isometric tension measurement and western blotting and the underlying mechanism. In addition, the effect of hypothermia on the contraction induced by voltage-operated calcium channel agonist KCl, Rho-kinase activator NaF, and PKC stimulant PDBu was examined to elucidate the underlying mechanism associated with hypothermia-mediated inhibition of dexmedetomidine-induced contraction. Furthermore, the effect of hypothermia on the myosin light chain (MLC20) and PKC phosphorylation, Rho-kinase membrane translocation induced by dexmedetomidine was examined to elucidate the involvement of the calcium-dependent and -sensitization mechanism associated with dexmedetomidine-induced contraction. Thus, this study offers a comprehensive examination of the effect of hypothermia on contraction induced by alpha-2 adrenoceptor agonist dexmedetomidine and the underlying mechanism.
Author Response File: Author Response.docx
