Systolic Blood Pressure Response to Orthostasis after Concussion is Related to ADRA2A Gene Receptor Subtypes

Abstract

Orthostasis causes a gravity-dependent redistribution of blood volume to the lower extremities. The baroreflex coordinates effector organs of the cardiovascular autonomic nervous system (CV-ANS) to produce a proportional response to mitigate an aberrant change in systolic blood pressure (SBP). In autonomic dysfunction (AD), there may be a lag or impaired accommodation leading to dramatic changes in SBP. Growing evidence indicates that AD is a part of the post-injury period after concussion. The impact of genetic variability of CV-ANS receptors including that of alpha-2 adrenoceptor (ADRA2A) gene polymorphisms remains undefined. PURPOSE: To evaluate the effect of ADRA2A gene variants on SBP responses to orthostasis in recently concussed athletes. METHODS: A prospective study was performed in 13 concussed college athletes (gender: 10 female, 3 male; age: 20±1 yrs; height: 1.70±0.11 m; weight: 74±17 kg). Beat-to-beat SBP was assessed digitally at rest for 10 minutes in the supine (SUP) position and then for 3 minutes in the standing (STND) position within 48 hours (48H) of concussion; SBP was averaged and a change score computed (ΔSBP = STND SBP - SUP SBP). Fast-Fourier transform was performed and power calculated for the low frequency (LF) spectra in each position (e.g., SUP LF-SBP, STND LF-SBP); the variables were log10 transformed for parametric analyses. A saliva sample was obtained from each participant and a commercial laboratory identified the ADRA2A single nucleotide polymorphism (rs1800544) using PMR-array. RESULTS: Data are presented as group mean (±SD). There were no ADRA2A [C/C: n=5; C/G: n=5, G/G: n=3) group differences for demographics, SUP and STND SBP or LF-SBP. A significant group main effect (p<0.05) was observed for ΔSBP and post-hoc tests revealed that the G/G [-21(±3)] response was significantly (p<0.05) lower than the C/G [7(±18)] group. A 3 X 2 RMANOVA for LF-SBP was performed. A significant group, position and interaction effect (p<0.05) was observed; post-hoc tests were not significant, but trending for an effect in the G/G group. CONCLUSION: The ADRA2A receptor, whose activation is known to inhibit the release of norepinephrine and reduce peripheral vasoconstriction, contributed to a blunted SBP response to orthostasis in G/G homozygotes compared to other variants within 48H of concussion.