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Time-Phasic Development of Nitrate Tolerance According to the Hemodynamic Responses and the Expression of Phosphodiesterase 1A1

 Dongsoo Kim  ;  Bum Kee Hong  ;  Eui-Young Choi  ;  Hyuck Moon Kwon  ;  Dong-Yun Kim  ;  Sung Woo Kwon  ;  Sung Ju Lee  ;  Jong Kwan Park  ;  Young Won Yoon  ;  Hyun-Seung Kim 
 KOREAN CIRCULATION JOURNAL, Vol.35 : 94-99, 2005 
Journal Title
Issue Date
Nitrates;Hemodynamic phenomena;Phosphodiesterases;Aorta
Background and Objectives:Time-phasic development of nitrate tolerance in cardiovascular diseases is very important because it can contribute to the advent of blunted vasodilation or rebound ischemia even during continuous NTG treatment. In such a condition, we should change the therapeutic regimen of nitrate treatment to prevent the worsening of symptoms. Materials and Methods:We created a nitrate-tolerant rat model using an osmotic minipump, and we examined the hemodynamic response to bolus NTG infusion in vivo. We checked the phosphodiesterase (PDE)1A1 mRNA and protein level by relative quantitative RT-PCR and western blot analysis. We used 8-cpt-cGMP for investigating the development of a time-phasic nitrate tolerance mechanism after nitrate infusion. Results:NTG-treated rats revealed a significant decrease in NTG-induced MAP drop (nitrate tolerance) from 1-day and this continued to the third day. The mRNA and protein levels of PDE1A1 similarly increased during these periods. Conclusion:This study revealed the development of time-phasic nitrate tolerance from the the aspects of in vivo hemodynamic responses and PDE 1A1 gene expression, and our work supports the need for further investigation to come up with a different therapeutic strategy and new drugs.
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1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Hyuck Moon(권혁문) ORCID logo https://orcid.org/0000-0001-9901-5015
Kim, Dong Soo(김동수)
Yoon, Young Won(윤영원) ORCID logo https://orcid.org/0000-0002-0907-0350
Lee, Youn Woo(이윤우)
Choi, Eui Young(최의영) ORCID logo https://orcid.org/0000-0003-3732-0190
Hong, Bum Kee(홍범기) ORCID logo https://orcid.org/0000-0002-6456-0184
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