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. 2014 Sep 11;4(3):775-89.
doi: 10.3390/metabo4030775.

Diltiazem reduces mortality and breakdown of ATP in red blood cell induced by isoproterenol in a freely moving rat model in vivo

Pollen K F Yeung  1 , Zhaolin Xu  2 , Dena Seeto  3
Affiliations

Diltiazem reduces mortality and breakdown of ATP in red blood cell induced by isoproterenol in a freely moving rat model in vivo

Pollen K F Yeung et al. Metabolites. .

Abstract

The benefit of calcium channel blockers for cardiovascular prevention against heart attack and stroke has not been firmly supported. We investigated the possible cardiovascular protective effect of diltiazem (DTZ) against injury induced by isoproterenol using a freely moving rat model in vivo. Sprague Dawley rats were injected subcutaneously (sc) with either 5 or 10 mg/kg of DTZ, or saline as control, twice daily for five doses. One hour after the last injection, a single dose of isoproterenol (30 mg/kg) was injected sc to each rat. Blood samples were collected serially for 6 h for measurement of adenine nucleotides (ATP, ADP and AMP) in red blood cell (RBC) by a validated HPLC. The study has shown isoproterenol induced 50% mortality and also increased RBC concentrations of AMP from 0.04 ± 0.02 to 0.29 ± 0.21 mM at the end of the experiment (p < 0.05). Treatment with 10 mg/kg of DTZ reduced mortality from 50% to <20% and attenuated the increase of RBC concentrations of AMP from +0.25 ± 0.22 in the control rats to +0.072 ± 0.092 mM (p < 0.05). The study concluded that 10 mg/kg of DTZ reduced mortality and breakdown of ATP induced by isoproterenol in rats.

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Figures

Figure 1
Figure 1
Hemodynamic effect of DTZ in rats treated with isoproterenol (30 mg/kg). Each point represents mean and SEM (n = 6 for DTZ 10 mg/kg Group; n = 10 for Normal Saline Group; n = 11 for No ISO Group). Abbreviations: DBP = diastolic blood pressure; SBP = systolic blood pressure; ISO = isoproterenol; DTZ = diltiazem.
Figure 2
Figure 2
Effect of DTZ on red blood cell concentrations of adenine nucleotides in rats treated with isoproterenol (30 mg/kg). Each point represents mean and SEM (n = 6 for DTZ 10 mg/kg Group; n = 10 for Normal Saline Group; n = 11 for No ISO Group).
Figure 3
Figure 3
Correlations between mean red blood cell concentrations of adenine nucleotides in rats (n = 6 for DTZ 10 mg/kg Group; n = 11 for Control Group D; n = 5 in the Survivors in Control Group; and n = 5 in the Non-Survivors in Control Group). Abbreviations: RBC = red blood cell; DTZ = diltiazem.
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