Activation Of Adenosine A2A Receptors Causes Hypotension In Newborn But Not Adult Rats

Abstract

Hypotension is very common in premature infants and has been associated with poor neurodevelopmental outcome although the underlying pathophysiology is unclear. Activation of central adenosine A2A receptors in decerebrate, vagotomized newborn piglets caused hypotension. We hypothesized that over‐expression of adenosine A2A receptors predisposes newborns to hypotension. We aimed to test this hypothesis by examining the effect of intraperitoneal injection (IP) of adenosine A2A receptor agonist CGS 21680 (CGS) on blood pressure (BP) in awake, non‐restrained maturing rats. BP was measured using a non‐invasive cuff blood pressure system, sphygmomanometery, on rat tail (PanLab, Spain). After 30 minutes of acclimatization in appropriate size chambers BP was measured before and one hour after IP CGS (4 mg/kg). CGS caused a significant decrease in systolic and diastolic BP in animals up to 6 weeks of life (n=13) but not adult rats (n=2). The systolic and diastolic BP decreased from 118±4 and 83±3 mmHg before CGS to 96±5 and 65±3 mmHg after CGS, respectively, p <0.001. Additionally, CGS caused a significant increase in heart rate from 426±7 to 528±14 before and after CGS, respectively, p < 0.001. We conclude that activation of adenosine A2A receptors causes hypotension in young but not adult rats. We speculate that over‐expression of adenosine A2A receptors early in life predisposes preterm infants to hypotension.