Adenosine infusion increases plasma levels of VEGF in humans

Abstract

Background: Many in vitro studies have shown that adenosine (Ado) can induce vascular endothelial growth factor (VEGF) mRNA and protein expression and stimulate endothelial proliferation. In the present study, we seek to determine whether Ado can increase circulating levels of VEGF protein in the intact human.

Methods: Five outpatients 49.3 +/- 6.7 years of age and weighing 88.2 +/- 8.5 kg were selected. They were given a 6 min intravenous infusion of Ado (0.14 mg kg-1 min-1) in conjunction with sestamibi myocardial perfusion scans. Mean blood pressure (MBP, calculated from systolic and diastolic values) and heart rate (HR) were determined before Ado infusion and every 2 min for the next 10 min. Plasma VEGF concentrations (ELISA) were determined immediately before Ado infusion and 1 h, 2 h, and 8 h after the infusion.

Results: Plasma VEGF concentration averaged 20.3 +/- 2.0 pg ml-1 prior to Ado infusion, and increased to 62.7 +/- 18.1 pg ml-1 at 1 h post- infusion (p < 0.01). VEGF plasma concentration returned to basal levels 2 h after infusion (23.3 +/- 3.4 pg ml-1). MBP averaged 116 +/- 7 mmHg and heart rate averaged 70 +/- 7 prior to Ado infusion. MBP decreased by a maximum of approximately 22% and HR increased by a maximum of approximately 17% during the infusion.

Conclusion: We conclude from these preliminary findings that intravenous infusion of adenosine can increase plasma levels of VEGF in humans.

Figure 1

Effect of adenosine on plasma VEGF protein concentration. Adenosine (0.14 mg kg^-1 min^-1) was infused intravenously for 6 minutes at 0 h. Panel A: Adenosine caused plasma VEGF protein concentration to increase by an average of ~3-fold at 1 h post-infusion. Plasma VEGF protein levels at 0, 1, 2, and 8 h were 20.3 ± 2.0, 62.7 ± 18.1, 23.3 ± 3.4, and 24.3 ± 7.0 pg ml^-1, respectively. Panel B: Adenosine caused plasma levels of VEGF protein to increase in all 5 subjects one h after the infusion; however, the response was relatively small in two subjects. Bars are means ± S.E.M. (n = 5 for each bar). Asterisks indicate p < 0.01.

Figure 2

Mean blood pressure (MBP) was calculated from systolic and diastolicpressures for the 5 patients (P₁–P₅). MBP was measured before Ado infusion (time 0), and then every 2 min for the next 10 min, except in P₃ in which a 10 min MBP was not obtained. Ado infusion caused MBP to decrease at some point during the infusion in all subjects, but the pressure did not decrease below 69 mmHg in any of the subjects.