Coenzyme Q10 (CoQ10) is a naturally occurring anti-oxidant increasingly used as a dietary supplement to enhance cardiovascular health. The objective of the current research was to study the effect of CoQ10 on cardiovascular hemodynamics and ATP metabolism in the red blood cells (RBC). Normotensive Sprague Dawley rats (SDR) with an implanted carotid artery catheter, weighing between 250 and 300 g were each housed in a freely moving caging environment with free access to drinking water. CoQ10 was dissolved in a vehicle made up of dimethyl sulfoxide (DMSO) and normal saline (1:1) for injection (5 mg/mL). Each rat received 4 doses of either 10 mg/kg of CoQ10 or the vehicle (n = 8 in each group) twice daily by subcutaneous (sc) injection. Blood samples (0.3 mL each) were collected before the injection of the last dose (T0), and at 0.08, 0.25 and 1 hour after the last dose for measurement of RBC concentrations of ATP and its catabolites by a validated high performance liquid chromatography assay (HPLC). Hemodynamic recordings were collected continuously throughout the experiment. Data between the two groups were compared and differences considered significant at p < 0.05 (Student’s t-test). Systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) before the last CoQ10 injection was significantly lower in the CoQ10 treatment group (SBP 124 ± 3 vs 137 ± 3 mm Hg; DBP 101 ± 3 vs 111 ± 4 and HR 414 ± 6 vs 440 ± 7 bpm (p < 0.05)). The RBC concentrations of ATP were higher in the CoQ10 treatment group (1.97 ± 0.28 vs 1.13 ± 0.23 mM, p < 0.05). However, the acute effect on hemodynamics or RBC ATP concentrations measured up to 1 hour after the last injection was not significant (p > 0.05 by paired t-test). It was concluded CoQ10 decreased BP and HR and increased RBC concentrations of ATP after multiple doses in normotensive rats.

BackgroundATP is a pivotal mediator and regulator of numerous cellular functions and plays an important role in cardiovascular homeostasis. We investigate the feasibility of exploiting ATP metabolism in the red blood cells (RBC) as systemic biomarker for cardiovascular protection.MethodsSprague Dawley rats (SDR) weighing between 250 and 300g were used. Each SDR had free access to drinking water during experiment. They were randomly divided into 3 groups. Group A (n = 10) received normal saline (NS), group B (n = 6) received diltiazem (DTZ) 10 mg/kg by subcutaneous (sc) injection twice daily for 4 doses, and group C (n = 8) received an exercise on a treadmill at 14 m/min for 15 minutes at 22% grade. One hour after the last dose of DTZ or NS or two hours after the exercise, each SDR received isoproterenol (ISO) (30 mg/kg) by sc injection. A separate control group (D) received no isoproterenol (n = 11). Hemodynamic recording (SBP, DBP, and HR) was collected continuously during the experiment. Data were analysed using t-tests and difference between groups considered significant at p < 0.05.ResultsISO induced 50% mortality within 5 hours after injection in the control group A (p < 0.05). It decreased SBP and DBP immediately after the injection (< 15 min) by -64 ± 20 and -61 ± 19 mmHg, respectively, but increased HR by +70 ± 53 bpm which was further increased to +157 ± 56 bpm by the end of the experiment (p < 0.05). Both SBP and DBP rebounded to pre-treatment level after 1-2 hours following injection (p < 0.05), and then continued to fall for the remaining of the experiment. Mortality was <20% (1 out of 6) in B, and 25% (2 out of 8) in the exercise group C, and none in group D. There was significant breakdown of ATP in the RBC in the NS treated group A (AUC of AMP/ATP = 0.12 ± 0.12 in A vs 0.03 ± 0.02 in D). Both exercise and DTZ (i.e. B and C) attenuated the breakdown of ATP induced by ISO (p < 0.05), but only exercise significantly reduced the rebound of blood pressure.ConclusionAcute myocardial infarction induced by ISO alters ATP metabolism in RBC which may be used to assess the effectiveness of cardiovascular protection from exercise and anti-ischemia drugs.CIHR, NSHRF and Dalhousie Pharmacy Endowment Foundation BackgroundATP is a pivotal mediator and regulator of numerous cellular functions and plays an important role in cardiovascular homeostasis. We investigate the feasibility of exploiting ATP metabolism in the red blood cells (RBC) as systemic biomarker for cardiovascular protection. ATP is a pivotal mediator and regulator of numerous cellular functions and plays an important role in cardiovascular homeostasis. We investigate the feasibility of exploiting ATP metabolism in the red blood cells (RBC) as systemic biomarker for cardiovascular protection. MethodsSprague Dawley rats (SDR) weighing between 250 and 300g were used. Each SDR had free access to drinking water during experiment. They were randomly divided into 3 groups. Group A (n = 10) received normal saline (NS), group B (n = 6) received diltiazem (DTZ) 10 mg/kg by subcutaneous (sc) injection twice daily for 4 doses, and group C (n = 8) received an exercise on a treadmill at 14 m/min for 15 minutes at 22% grade. One hour after the last dose of DTZ or NS or two hours after the exercise, each SDR received isoproterenol (ISO) (30 mg/kg) by sc injection. A separate control group (D) received no isoproterenol (n = 11). Hemodynamic recording (SBP, DBP, and HR) was collected continuously during the experiment. Data were analysed using t-tests and difference between groups considered significant at p < 0.05. Sprague Dawley rats (SDR) weighing between 250 and 300g were used. Each SDR had free access to drinking water during experiment. They were randomly divided into 3 groups. Group A (n = 10) received normal saline (NS), group B (n = 6) received diltiazem (DTZ) 10 mg/kg by subcutaneous (sc) injection twice daily for 4 doses, and group C (n = 8) received an exercise on a treadmill at 14 m/min for 15 minutes at 22% grade. One hour after the last dose of DTZ or NS or two hours after the exercise, each SDR received isoproterenol (ISO) (30 mg/kg) by sc injection. A separate control group (D) received no isoproterenol (n = 11). Hemodynamic recording (SBP, DBP, and HR) was collected continuously during the experiment. Data were analysed using t-tests and difference between groups considered significant at p < 0.05. ResultsISO induced 50% mortality within 5 hours after injection in the control group A (p < 0.05). It decreased SBP and DBP immediately after the injection (< 15 min) by -64 ± 20 and -61 ± 19 mmHg, respectively, but increased HR by +70 ± 53 bpm which was further increased to +157 ± 56 bpm by the end of the experiment (p < 0.05). Both SBP and DBP rebounded to pre-treatment level after 1-2 hours following injection (p < 0.05), and then continued to fall for the remaining of the experiment. Mortality was <20% (1 out of 6) in B, and 25% (2 out of 8) in the exercise group C, and none in group D. There was significant breakdown of ATP in the RBC in the NS treated group A (AUC of AMP/ATP = 0.12 ± 0.12 in A vs 0.03 ± 0.02 in D). Both exercise and DTZ (i.e. B and C) attenuated the breakdown of ATP induced by ISO (p < 0.05), but only exercise significantly reduced the rebound of blood pressure. ISO induced 50% mortality within 5 hours after injection in the control group A (p < 0.05). It decreased SBP and DBP immediately after the injection (< 15 min) by -64 ± 20 and -61 ± 19 mmHg, respectively, but increased HR by +70 ± 53 bpm which was further increased to +157 ± 56 bpm by the end of the experiment (p < 0.05). Both SBP and DBP rebounded to pre-treatment level after 1-2 hours following injection (p < 0.05), and then continued to fall for the remaining of the experiment. Mortality was <20% (1 out of 6) in B, and 25% (2 out of 8) in the exercise group C, and none in group D. There was significant breakdown of ATP in the RBC in the NS treated group A (AUC of AMP/ATP = 0.12 ± 0.12 in A vs 0.03 ± 0.02 in D). Both exercise and DTZ (i.e. B and C) attenuated the breakdown of ATP induced by ISO (p < 0.05), but only exercise significantly reduced the rebound of blood pressure. ConclusionAcute myocardial infarction induced by ISO alters ATP metabolism in RBC which may be used to assess the effectiveness of cardiovascular protection from exercise and anti-ischemia drugs.CIHR, NSHRF and Dalhousie Pharmacy Endowment Foundation Acute myocardial infarction induced by ISO alters ATP metabolism in RBC which may be used to assess the effectiveness of cardiovascular protection from exercise and anti-ischemia drugs.