Multiple activation mechanisms of serotonin-mediated contraction in the carotid arteries obtained from spontaneously hypertensive rats

Shun Watanabe, Takayuki Matsumoto, Makoto Ando, Tsuyuki Adachi, Shota Kobayashi, Maika Iguchi, Miki Takeuchi, Kumiko Taguchi, Tsuneo Kobayashi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is an important endogenous substance that regulates the vascular tone, and the abnormal signaling of 5-HT has been observed in the arteries under several pathophysiological conditions such as diabetes and hypertension. However, signaling pathways of 5-HT-mediated vasocontraction in hypertension remain unclear. Therefore, we tested the hypothesis that 5-HT-mediated contraction and contributions of various kinases such as mitogen-activated protein kinases (MAPKs), phosphoinositide 3-kinase (PI3K), Rho kinase (ROCK), and 3-phosphoinositide-dependent kinase 1 (PDK1) to the contraction would be altered in the carotid arteries obtained from spontaneously hypertensive rats (SHR) compared to control Wistar Kyoto (WKY) rats. In the carotid arteries from SHR (vs. those from WKY), (1) the 5-HT-mediated contraction was increased, whereas the norepinephrine-mediated contraction was not; (2) 5-HT-mediated contractions were partly inhibited by each kinase (extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, c-Jun N-terminal kinase (JNK), PI3K, ROCK, and PDK1) inhibitor; and (3) 5-HT-stimulated phosphorylation of ERK1/2, p38 MAPK, JNK, myosin phosphatase target subunit 1 (MYPT1), and PDK1 was increased. The expression of ROCK2 but not ROCK1 was increased in the carotid arteries from SHR compared to WKY. The expression of 5-HT2A receptor, a major receptor of 5-HT-mediated contraction in rat carotid artery, was similar in carotid arteries between the two groups. These results suggest that 5-HT-mediated contraction was utilized multiple signaling pathways such as ERK1/2, p38 MAPK, JNK, PI3K, ROCK, and PDK1. Although 5-HT-mediated contraction was increased in the carotid arteries obtained from SHR, further studies are necessary to clarify how each kinase may integrate in the vascular smooth muscles under hypertension.

Original languageEnglish
Pages (from-to)1271-1282
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume468
Issue number7
DOIs
Publication statusPublished - 2016 Jul 1
Externally publishedYes

Keywords

  • 5-HT
  • Carotid artery
  • Contraction
  • Hypertension
  • Kinase
  • PDK1

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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