The Open Drug Metabolism Journal

2011, 5 : 1-6
Published online 2011 June 10. DOI: 10.2174/1874073101105010001
Publisher ID: TODMJ-5-1

RESEARCH ARTICLE
 Anti-Ischemia Drugs have no Effect on the Metabolism of ATP by RBC in Normotensive Restrained Rats

Pollen K.F. Yeung, * , Julie Dauphinee , Krista Simonson and Thera Gouzoules

* Address correspondence to this author at the College of Pharmacy, 5968 College Street, Burbidge Building, Dalhousie University, Halifax, NS, B3H 3J5, Canada; Tel: 902-4943845; Fax: 902-4941396; E-mail: pollen.yeung@dal.ca

ABSTRACT

The objective is to determine the effect of anti-ishemia agents on metabolism of adenosine-5'-triphosphate (ATP) in red blood cell (RBC) in a normotensive rat model. Male Sprague Dawley (SD) rats weighing between 300 - 400 g were used. Each rat received either saline (control), or 5 mg/kg of diltiazem (DTZ), losartan, amlodipine or dipyridamole by subcutaneous injection (sc) twice daily for 5 doses. Blood samples were collected using a “Stopping Solution” from each rat at time 0 (before the last dose), and sequentially after over 6 hours following the last dose via an indwelling carotid artery catheter. In addition, hemodynamic recordings were collected throughout the experiment. Concentrations of ATP and other purine nucleotides in the RBC were determined by a validated HPLC. Data between groups were analyzed by ANOVA and paired t-test, and differences between groups considered significant when p < 0.05. The results showed that the concentrations of ATP and the other purine nucleotides in RBC of the rats treated with the anti-ischemia drugs were not different from the control rats (Table 1). The concentrations of ATP and guanosine-5'-triphosphate (GTP) were higher towards the end of the experiment, but the increase was significant only after amlodipine and losartan (p < 0.05). The increase of ATP and AMP concentrations correlated with decrease of diastolic blood pressure (DBP) in the rats. The study concluded that the anti-ischemia drugs tested in the current study have no effect on RBC concentrations of ATP in the restraining rat model

Keywords:

ATP, purine nucleotides, metabolism, biomarkers, anti-ischemia drugs, diltiazem.