Sympathetic nonadrenergic transmission contributes to autonomic dysreflexia in spinal cord-injured individuals.
Autonomic dysreflexia is a hypertensive episode in spinal cord-injured individuals induced by exaggerated sympathetic activity and thought to be alpha-adrenergic mediated. alpha-Adrenoceptor antagonists have been a rational first choice; nevertheless, calcium channel blockers are primarily used in autonomic dysreflexia management. However, alpha-adrenoceptor blockade may leave a residual vasoconstrictor response to sympathetic nonadrenergic transmission unaffected. The aim was to assess the alpha-adrenergic contribution and, in addition, the role of supraspinal control to leg vasoconstriction during exaggerated sympathetic activity provoked by autonomic dysreflexia in spinal cord-injured individuals and by a cold pressure test in control individuals. Upper leg blood flow was measured using venous occlusion plethysmography during supine rest and during exaggerated sympathetic activity in 6 spinal cord-injured individuals and 7 able-bodied control individuals, without and with phentolamine (alpha-adrenoceptor antagonist) and nicardipine (calcium channel blocker) infusion into the right femoral artery. Leg vascular resistance was calculated. In spinal cord-injured individuals, phentolamine significantly reduced the leg vascular resistance increase during autonomic dysreflexia (8+/-5 versus 24+/-13 arbitrary units; P=0.04) in contrast to nicardipine (15+/-10 versus 24+/-13 arbitrary units; P=0.12). In controls, phentolamine completely abolished the leg vascular resistance increase during a cold pressure test (1+/-2 versus 18+/-14 arbitrary units; P=0.02). The norepinephrine increase during phentolamine infusion was larger (P=0.04) in control than in spinal cord-injured individuals. These results indicate that the leg vascular resistance increase during autonomic dysreflexia in spinal cord-injured individuals is not entirely alpha-adrenergic mediated and is partly explained by nonadrenergic transmission, which may, in healthy subjects, be suppressed by supraspinal control.
Groothuis
Jan T
JT
Department of Physiology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Rongen
Gerard A
GA
Deinum
Jaap
J
Pickkers
Peter
P
Danser
A H Jan
AH
Geurts
Alexander C H
AC
Smits
Paul
P
Hopman
Maria T E
MT
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000097:blood; D020211:Autonomic Dysreflexia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D006801:Humans; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000008:administration & dosage; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000008:administration & dosage*; D010991:Plethysmography; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012083:Renin / Q000097:blood; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D011942:Receptors, Adrenergic, alpha; D000804:Angiotensin II; D009529:Nicardipine; D012083:Renin; D009638:Norepinephrine; D010646:Phentolamine