Home General Physiology and Biophysics 2023 General Physiology and Biophysics Vol.42, No.6, p. 469–478, 2023

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Founded: 1982
ISSN  1338-4325 (online)

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General Physiology and Biophysics Vol.42, No.6, p. 469–478, 2023

Title: Theophylline-induced endothelium-dependent vasodilation is mediated by increased nitric oxide release and phosphodiesterase inhibition in rat aorta
Author: Kyeong-Eon Park, Soo Hee Lee, Sung Il Bae, Yeran Hwang, Seong-Ho Ok, Seung Hyun Ahn, Gyujin Sim, Soonghee Chung, Ju-Tae Sohn

Abstract: This study aimed to examine the endothelial dependence of vasodilation induced by the phosphodiesterase inhibitor theophylline in isolated rat thoracic aortas and elucidate the underlying mechanism, with emphasis on endothelial nitric oxide (NO). The effects of various inhibitors and endothelial denudation on theophylline-induced vasodilation, and the effect of theophylline on vasodilation induced by NO donor sodium nitroprusside, cyclic guanosine monophosphate (cGMP) analog bromo-cGMP, and β-agonist isoproterenol in endothelium-denuded aorta were examined. The effects of theophylline and sodium nitroprusside on cGMP formation were also examined. We examined the effect of theophylline on endothelial nitric oxide synthase (eNOS) phosphorylation and intracellular calcium levels. Theophylline-induced vasodilation was greater in endothelium-intact aortas than that in endothelium-denuded aortas. The NOS inhibitor, NW-nitro-L-arginine methyl ester; non-specific guanylate cyclase (GC) inhibitor, methylene blue; and NO-sensitive GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one inhibited theophylline-induced vasodilation in endothelium-intact aortas. Theophylline increased the vasodilation induced by sodium nitroprusside, bromo-cGMP, and isoproterenol. Theophylline increased cGMP formation in endothelium-intact aortas, and sodium nitroprusside-induced cGMP formation in endothelium-denuded aortas. Moreover, theophylline increased stimulatory eNOS (Ser1177) phosphorylation and endothelial calcium levels, but decreased the phosphorylation of inhibitory eNOS (Thr495). These results suggested that theophylline-induced endothelium-dependent vasodilation was mediated by increased endothelial NO release and phosphodiesterase inhibition.

Keywords: Theophylline — Nitric oxide — Endothelium — Phosphodiesterase — Vasodilation
Published online: 23-Oct-2023
Year: 2023, Volume: 42, Issue: 6 Page From: 469, Page To: 478

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