Int J Med Sci 2020; 17(1):21-32. doi:10.7150/ijms.39074 This issue Cite

Research Paper

Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase

Soo Hee Lee1*, Seong-Ho Ok2*, Raghavendra Baregundi Subbarao1, Ji-Yoon Kim3, Sung Il Bae3, Yeran Hwang3, Seongyeong Tak3, Ju-Tae Sohn1,4✉

1. Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea.
2. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon, 51427, Republic of Korea.
3. Department of Anesthesiology and Pain Medicine, Gyeongsang National University Hospital, 15 Jinju-daero 816 beon-gil, Jinju-si, Gyeongsangnam-do, 52727, Republic of Korea.
4. Institute of Health Sciences, Gyeongsang National University, Jinju-si, 52727, Republic of Korea.
*These authors contributed equally to the work

Citation:
Lee SH, Ok SH, Subbarao RB, Kim JY, Bae SI, Hwang Y, Tak S, Sohn JT. Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase. Int J Med Sci 2020; 17(1):21-32. doi:10.7150/ijms.39074. https://www.medsci.org/v17p0021.htm
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Abstract

This study examined the possible upstream cellular signaling pathway associated with nitric oxide (NO)-mediated inhibition of phenylephrine-induced contraction in isolated rat aortae in response to mild hypothermia, with a particular focus on endothelial Rho-kinase. We examined the effects of mild hypothermia (33°C), wortmannin, Nω-nitro-L-arginine methyl ester (L-NAME), Y-27632, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and methylene blue, alone and combined, on phenylephrine-induced contraction in isolated rat aortae. Finally, we examined the effects of mild hypothermia, wortmannin, Y-27632 and L-NAME, alone and combined, on endothelial nitric oxide synthase (eNOS) and endothelial Rho-kinase membrane translocation induced by phenylephrine. Mild hypothermia attenuated phenylephrine-induced contraction only in endothelium-intact aortae. L-NAME, wortmannin, ODQ and methylene blue increased phenylephrine-induced contraction of endothelium-intact aortae pretreated at 33°C. Wortmannin did not significantly alter the L-NAME-induced enhancement of phenylephrine-induced maximal contraction of endothelium-intact aortae pretreated at 33°C. Wortmannin abolished the ability of Y-27632 to magnify the hypothermic inhibition of maximal phenylephrine-induced contraction. Wortmannin and L-NAME inhibited the enhancing effect of mild hypothermia on phenylephrine-induced eNOS phosphorylation. Y-27632 and L-NAME attenuated the enhancing effect of hypothermia on phenylephrine-induced endothelial Rho-kinase membrane translocation. The results suggest that hypothermia-induced, NO-dependent inhibition of phenylephrine-induced contraction is mediated by phosphoinositide 3-kinase and inhibited by endothelial Rho-kinase activation.

Keywords: hypothermia, nitric oxide, phenylephrine, endothelial Rho-kinase, contraction, aorta, phosphoinositide 3-kinase


Citation styles

APA
Lee, S.H., Ok, S.H., Subbarao, R.B., Kim, J.Y., Bae, S.I., Hwang, Y., Tak, S., Sohn, J.T. (2020). Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase. International Journal of Medical Sciences, 17(1), 21-32. https://doi.org/10.7150/ijms.39074.

ACS
Lee, S.H.; Ok, S.H.; Subbarao, R.B.; Kim, J.Y.; Bae, S.I.; Hwang, Y.; Tak, S.; Sohn, J.T. Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase. Int. J. Med. Sci. 2020, 17 (1), 21-32. DOI: 10.7150/ijms.39074.

NLM
Lee SH, Ok SH, Subbarao RB, Kim JY, Bae SI, Hwang Y, Tak S, Sohn JT. Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase. Int J Med Sci 2020; 17(1):21-32. doi:10.7150/ijms.39074. https://www.medsci.org/v17p0021.htm

CSE
Lee SH, Ok SH, Subbarao RB, Kim JY, Bae SI, Hwang Y, Tak S, Sohn JT. 2020. Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase. Int J Med Sci. 17(1):21-32.

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