A Study of the Effect of Isoproterenol on Red Blood Cell Concentrations of Adenine Nucleotides in a Freely Moving Rat Model In Vivo*

Abstract

Previous studies have shown that red blood cell (RBC) concentrations of adenine 5'-triphosphate (ATP) may be a key factor for post exercise effects responsible for cardiovascular protection. To test this concept further, we investigated the effect of isoproterenol on ATP metabolism in RBC using a freely moving rat model in vivo. Sprague Dawley rats were given either isoproterenol (30 mg/kg) or saline by subcutaneous (sc) injection. Blood samples were collected sequentially for up to 6 hours for measurement of adenine nucleotides in the RBC. Hemodynamic recordings were collected throughout the experiment. We have found isoproterenol induced 50% mortality under the experimental condition. It decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) immediately after the injection by -64 ± 22 and -64 ± 20 mmHg in less than 15 min, and increased HR steadily by +158 ± 59 bpm at the end of the experiment. Isoproterenol also increased RBC concentrations of adenine 5'-monophosphate (AMP) from 0.04 ± 0.01 to 0.28 ± 0.23 mM (+500%). The rats died had much greater breakdown of ATP to adenosine 5'-monophosphate (AMP) in the RBC than those surviving from the injury (p<0.05 for all the comparison).

Diltiazem Reduces Mortality and Breakdown of ATP in Red Blood Cell Induced by Isoproterenol in a Freely Moving Rat Model in Vivo

“…50%), profoundly altered the cardiovascular hemodynamics, and significantly increased RBC concentrations of AMP. In the rats which could not survive the effects, there was a steeper rebound in systolic and diastolic blood pressures following the immediate fall, and a significant increase in break down of ATP to AMP in the RBC than the surviving rats [ 20 ]. It appears that 10 mg/kg of DTZ given twice daily for 5 doses improved survival rate and significantly reduced the AMP concentrations and the AUC ratio of AMP to ATP, which is a measure of catabolism of ATP to AMP in RBC ( Table 2 ).…”

“…The heart rate was increased immediately and stayed elevated throughout the experiment. In addition, isoproterenol also increased RBC concentrations of adenosine 5’-monophosphate (AMP), and those rats did not survive from the acute MI had much higher concentrations of AMP [ 20 ]. However the study did not assess possible modulation by pharmacologic agents.…”

“…However the study did not assess possible modulation by pharmacologic agents. The current study is aimed to follow up the previous study and investigate a possible mechanism for the cardiovascular protective effect of DTZ against injury induced by isoproterenol using a freely moving rat model in vivo as described previously [ 20 , 21 ].…”

Therapeutic Potential of Adenosine Transport Modulators for Cardiovascular Protection

“…While most of the earlier studies have focused on the effect of NTI on extracellular adenosine or adenosine metabolism in cardiac myocytes, little is known of the effect of these agents on ATP/adenosine metabolism in erythrocytes (RBC) in vivo under normal or in ischemia conditions. It is probable that the increase in plasma concentrations of adenosine during ischemia could be attributed at least in part to metabolic breakdown of ATP in the RBC [40]. Blockade of the reuptake of adenosine by the NTI could moderate ATP metabolism and the nucleotide pool in the RBC which may be an important factor affecting the safety and efficacy of these therapeutic agents.…”

Natural Health Products as Modulators of Adenosine and ATP Metabolism for Cardiovascular Protection

“…ADP and AMP) [15]. This can cause an increase in adenosine production in the myocytes, vascular endothelium, smooth muscle cells [16] and in the RBC [17]. The adenosine released into the circulation is taken up rapidly by endothelial cells and red blood cells via nucleoside transporters and subsequently metabolized [18,19].…”