Liqin Huo1, Jingze Zhang2, Zhuo Qu1, Hong Chen3, Yuming Li4, Wenyuan Gao5. 1. School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China. 2. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China; Department of Pharmacy, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China. 3. Department of Pharmacy, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China. 4. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Logistics College of Chinese People's Armed Police Forces, Tianjin 300162, China. 5. School of Pharmaceutical Science and Technology, Tianjin University, Weijin Road, Tianjin 300072, China. Electronic address: pharmgao@tju.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Shunaoxin pill (SNX), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Xionggui". It has been used for treatment of cerebrovascular related diseases. It is well known that vasodilatation plays a very important role in cerebrovascular diseases. The effect of SNX on vasorelaxant activity has not yet been explored. Therefore, we aimed to investigate the vasorelaxant effects of SNX on isolated rat thoracic aorta so as to assess some of the possible mechanisms. We also investigate the gasotransmitter signaling pathway involved which has been rarely reported in isolated rat thoracic aorta before. AIM OF THE STUDY: The present study was performed to examine the vasodilative activity of SNX and its mechanisms in isolated rat thoracic aorta. MATERIALS AND METHODS: SNX was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including soluble guanylate cyclase (sGC) inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), cyclooxygenase (COX) inhibitor indomethacin (INDO), NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), heme oxygenase-1 (HO-1) inhibitor zinc-protoporphyrin (ZnPP), cystathionine γ-lyase (CSE) inhibitor DL-Propargylglycine (PAG), non-selective K(+) channel inhibitor tetraethylammonium chloride (TEA), KV channel inhibitor 4-Aminopyridine (4-AP), and KATP channel inhibitor Glibenclamide (Gli) were used, they were added 20min before NE contraction and then added SNX to induce vasodilation. RESULTS: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with L-NAME, ODQ or ZnPP significantly blocked SNX-induced relaxation. Pretreatment with the non-selective K(+) channel inhibitor TEA, KV channel inhibitor 4-AP or the KATP channel inhibitor Gli, none of them had influences on the SNX-induced response (p>0.05). Besides, SNX inhibited the contraction triggered by NE in endothelium-denuded rings in Ca(2+)-free medium. SNX also produced rightward parallel displacement of CaCl2 curves. CONCLUSIONS: These results suggest that SNX can induce less endothelium-dependent and more endothelium-independent vascular relaxation. The NO/cGMP and HO/CO pathways, blockade of Ca(2+) channels are inhibition of IP3R mediated Ca(2+) mobilization from intracellular stores, are likely involved in this relaxation. Furthermore, the underlying mechanisms of combined compositions in SNX await further investigations.
ETHNOPHARMACOLOGICAL RELEVANCE: Shunaoxin pill (SNX), one of the famous classical recipes in traditional Chinese medicine, is developed from the "Decoction of Xionggui". It has been used for treatment of cerebrovascular related diseases. It is well known that vasodilatation plays a very important role in cerebrovascular diseases. The effect of SNX on vasorelaxant activity has not yet been explored. Therefore, we aimed to investigate the vasorelaxant effects of SNX on isolated rat thoracic aorta so as to assess some of the possible mechanisms. We also investigate the gasotransmitter signaling pathway involved which has been rarely reported in isolated rat thoracic aorta before. AIM OF THE STUDY: The present study was performed to examine the vasodilative activity of SNX and its mechanisms in isolated rat thoracic aorta. MATERIALS AND METHODS:SNX was studied on isolated rat thoracic aorta in vitro, including endothelium-intact and endothelium-denuded aortic rings. In present study, specific inhibitors including soluble guanylate cyclase (sGC) inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ), cyclooxygenase (COX) inhibitor indomethacin (INDO), NO synthase inhibitor NG-nitro-l-arginine methyl ester (L-NAME), heme oxygenase-1 (HO-1) inhibitor zinc-protoporphyrin (ZnPP), cystathionine γ-lyase (CSE) inhibitor DL-Propargylglycine (PAG), non-selective K(+) channel inhibitor tetraethylammonium chloride (TEA), KV channel inhibitor 4-Aminopyridine (4-AP), and KATP channel inhibitor Glibenclamide (Gli) were used, they were added 20min before NE contraction and then added SNX to induce vasodilation. RESULTS: Removal of endothelium or pretreatment of aortic rings (intact endothelium) with L-NAME, ODQ or ZnPP significantly blocked SNX-induced relaxation. Pretreatment with the non-selective K(+) channel inhibitor TEA, KV channel inhibitor 4-AP or the KATP channel inhibitor Gli, none of them had influences on the SNX-induced response (p>0.05). Besides, SNX inhibited the contraction triggered by NE in endothelium-denuded rings in Ca(2+)-free medium. SNX also produced rightward parallel displacement of CaCl2 curves. CONCLUSIONS: These results suggest that SNX can induce less endothelium-dependent and more endothelium-independent vascular relaxation. The NO/cGMP and HO/CO pathways, blockade of Ca(2+) channels are inhibition of IP3R mediated Ca(2+) mobilization from intracellular stores, are likely involved in this relaxation. Furthermore, the underlying mechanisms of combined compositions in SNX await further investigations.