Korean Circ J.  2005 Jan;35(1):94-99. 10.4070/kcj.2005.35.1.94.

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

• Kim D
• Hong BK
• Choi EY
• Kwon HM
• Kim DY
• Kwon SW
• Lee SJ
• Park JK
• Yoon YW
• Kim HS

• KMID: 2093918
• DOI: http://doi.org/10.4070/kcj.2005.35.1.94

Abstract

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.

Keyword

Nitrates; Hemodynamic phenomena; Phosphodiesterases; Aorta

MeSH Terms

Animals
Aorta
Blotting, Western
Cardiovascular Diseases
Gene Expression
Hemodynamics*
Ischemia
Models, Animal
Nitrates
Phosphoric Diester Hydrolases
Rats
RNA, Messenger
Vasodilation
Nitrates
Phosphoric Diester Hydrolases
RNA, Messenger