Abnormal Pressure Stress Reduces Interleukin-1β-Induced Cyclooxygenase-2 Expression in Cultured Rat Vascular Smooth Muscle Cells

Takuji Machida; Tomoko Hinse Endo; Riho Oyoshi; Mikiko Yutani; Maiko Machida; Saki Shiga; Hina Murakami; Sachiko Hiraide; Masahiko Hirafuji; Kenji Iizuka

doi:10.1248/bpb.b21-00078

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Abnormal Pressure Stress Reduces Interleukin-1β-Induced Cyclooxygenase-2 Expression in Cultured Rat Vascular Smooth Muscle Cells

Takuji Machida , Tomoko Hinse Endo, Riho Oyoshi, Mikiko Yutani, Maiko Machida, Saki Shiga, Hina Murakami, Sachiko Hiraide, Masahiko Hirafuji, Kenji Iizuka

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Takuji Machida Corresponding author
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Tomoko Hinse Endo
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Riho Oyoshi
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Mikiko Yutani
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Maiko Machida
Division of Pharmacotherapy, Faculty of Pharmaceutical Sciences, Hokkaido University of Science
Saki Shiga
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Hina Murakami
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Sachiko Hiraide
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Masahiko Hirafuji
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido
Kenji Iizuka
Department of Pharmacological Sciences, School of Pharmaceutical Sciences, Health Sciences University of Hokkaido

Keywords: pulsatile pressure stress, cyclooxygenase-2, interleukin-1β, extracellular signal-regulated kinase, protein kinase C, vascular smooth muscle cell

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2021 Volume 44 Issue 6 Pages 853-860

DOI https://doi.org/10.1248/bpb.b21-00078

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Abstract

Elevated mechanical stress on blood vessels associated with hypertension has a direct effect on the function of vascular endothelial cells and vascular smooth muscle cells (VSMCs). In the present study, we have identified the effect of pulsatile pressure stress on cyclooxygenase-2 (COX-2) expression induced by interleukin (IL)-1β in cultured rat VSMCs. VSMCs were isolated from aortic media of Wistar rats and cultured. Pulsatile pressure applied to VSMCs was repeatedly given between either 80 and 160 mmHg, which simulates systolic hypertension, or 80 and 120 mmHg, which simulates normal blood pressure, at a frequency of 4 cycles per min using our original apparatus. Pressure loading that simulates systolic hypertension reduced IL-1β-induced COX-2 expression. The pressure also inhibited the rapid and transient phosphorylation of extracellular signal-regulated kinase (ERK) induced by IL-1β. IL-1β-induced COX-2 expression was significantly inhibited by a specific conventional protein kinase C (PKC) inhibitor. Pressure loading that simulates systolic hypertension also reduced phorbol myristate 13-acetate (PMA) (a PKC activator)-induced COX-2 expression and the rapid and transient phosphorylation of ERK. Pressure loading that simulates normal blood pressure had no effect on IL-1β- and PMA-induced COX-2 expression. The present study shows that pressure stress between 80 and 160 mmHg, which simulates systolic hypertension reduces IL-1β-induced COX-2 expression by affecting a mechanism involving PKC and ERK signaling pathways. Downregulation of COX-2 expression in VSMCs by abnormal pressure stress may further worsen local vascular injury associated with hypertension.

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