Abstract

Objectives: This study was designed to determine whether xanthine oxidoreductase (XOR) is involved in Isosorbide- 5-mononitrate (IS-5-MN) metabolism, and to elucidate the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the IS-5-MN response. Methods: In 15 Chinese volunteers, we observed the relationship between baseline XOR-mRNA expression in peripheral blood mononuclear cells (PBMCs) and the response to 20 mg IS-5-MN. IS-5-MN pharmacokinetics profiles, changes in plasma concentrations of CGRP, and CGRPmRNA expression in PBMCs were assessed in vivo and in vitro. Results: Individuals with a lower baseline XOR-mRNA expression showed lower plasma XOR activity and significantly greater changes in SBP (ΔSBP) after IS-5-MN administration. Individuals with a lower baseline XOR-mRNA expression also showed significantly greater increases in plasma concentrations of CGRP. There were no differences in IS-5-MN AUC between the two groups. IS-5-MN significantly up-regulated the expression of CGRP α- and CGRP β-mRNA in PBMCs, which were not affected by the XOR inhibitor allopurinol. Conclusions: Our study suggests that CGRP may contribute to the response to IS-5 MN in a XOR-independent pathway.

Author Details

Authors

• Zuoliang Liu²
• Bikui Zhang¹
• Xin Guo³
• Lei Chen⁴
• Dongyang Yi¹
• Junzi Cong⁵
• Ren Guo¹

Departments

• ¹ Department of Pharmacy,
• ² Department of ICU, The Third Xiangya Hospital, Central South University,
• ³ Taige Xiangya Drug research co., LTD,
• ⁴ Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, Hunan, and
• ⁵ Department of Pharmacology, The Hongqi Hospital of Mudanjiang, Mudanjiang, Heilongjiang, China

Address

Dr. Ren Guo
Department of Pharmacy,
The Third Xiangya Hospital, Central South University
Changsha, Hunan 410013, China
Email: [email protected]

Citation