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CGRP mediate the isosorbide-5-mononitrate cardiovascular response in healthy Chinese male volunteers through a XOR-independent pathway.
Int J Clin Pharmacol Ther. 2015 Apr; 53(4):325-34.IJ

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.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article

Language

eng

PubMed ID

25740261

Citation

Liu, Zuoliang, et al. "CGRP Mediate the Isosorbide-5-mononitrate Cardiovascular Response in Healthy Chinese Male Volunteers Through a XOR-independent Pathway." International Journal of Clinical Pharmacology and Therapeutics, vol. 53, no. 4, 2015, pp. 325-34.
Liu Z, Zhang B, Guo X, et al. CGRP mediate the isosorbide-5-mononitrate cardiovascular response in healthy Chinese male volunteers through a XOR-independent pathway. Int J Clin Pharmacol Ther. 2015;53(4):325-34.
Liu, Z., Zhang, B., Guo, X., Chen, L., Yi, D., Cong, J., & Guo, R. (2015). CGRP mediate the isosorbide-5-mononitrate cardiovascular response in healthy Chinese male volunteers through a XOR-independent pathway. International Journal of Clinical Pharmacology and Therapeutics, 53(4), 325-34. https://doi.org/10.5414/CP202178
Liu Z, et al. CGRP Mediate the Isosorbide-5-mononitrate Cardiovascular Response in Healthy Chinese Male Volunteers Through a XOR-independent Pathway. Int J Clin Pharmacol Ther. 2015;53(4):325-34. PubMed PMID: 25740261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CGRP mediate the isosorbide-5-mononitrate cardiovascular response in healthy Chinese male volunteers through a XOR-independent pathway. AU - Liu,Zuoliang, AU - Zhang,Bikui, AU - Guo,Xin, AU - Chen,Lei, AU - Yi,Dongyang, AU - Cong,Junzi, AU - Guo,Ren, PY - 2015/03/24/accepted PY - 2015/3/6/entrez PY - 2015/3/6/pubmed PY - 2015/8/19/medline SP - 325 EP - 34 JF - International journal of clinical pharmacology and therapeutics JO - Int J Clin Pharmacol Ther VL - 53 IS - 4 N2 - 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. SN - 0946-1965 UR - https://www.unboundmedicine.com/medline/citation/25740261/CGRP_mediate_the_isosorbide_5_mononitrate_cardiovascular_response_in_healthy_Chinese_male_volunteers_through_a_XOR_independent_pathway_ L2 - http://www.dustri.com/nc/journals-in-english?artId=13154 DB - PRIME DP - Unbound Medicine ER -