Spinal cord injury enhances arterial expression and reactivity of α1-adrenergic receptors-mechanistic investigation into autonomic dysreflexia

Abstract

Background context: Autonomic dysreflexia (AD) usually presents with a significant increase in blood pressure, and uncontrollable autonomic response to stimuli below the level of spinal cord injury (SCI).

Purpose: This study analyzed the vasomotor function and molecular changes in the peripheral arteries below the lesion of SCI to characterize the mechanism of autonomic dysreflexia.

Study design: This was a randomized experimental study in rats.

Methods: Contusive SCI was induced using a force-calibrated weight-drop device at the T10 level in anesthetized rats. Two weeks after severe SCI, blood flow in the femoral arteries was measured, and the vasomotor function and expression of α1-adrenergic receptors were analyzed.

Results: Blood flow in the femoral artery was significantly reduced in rats with SCI (8.0±2 vs. 17.5±4 mL/min, SCI vs. control, respectively; p=.016). The contraction responses of femoral artery segments to cumulative addition of α1-adrenergic agonist phenylephrine were significantly enhanced in rats with SCI. Expression of α1-adrenergic receptor was upregulated in the medial layer of femoral artery vascular homogenates of these rats.

Conclusion: Our study provides evidence demonstrating that prolonged denervation below the lesion level following SCI results in a compensatory increased expression of α1-adrenergic receptors in the arterial smooth muscle layer, thereby enhancing the responsiveness to α1-adrenergic agonist and potentiating the development of AD.

Keywords: Autonomic dysreflexia; Autonomic hyperreflexia; Hypertension; Neuroaxial denervation; Phenylephrine; Spinal cord injury; Sympathetic activity; Vascular smooth muscle; Vasoreactivity; α-1 adrenergic receptor.