Angiotensin-converting enzyme (ACE) inhibitors exacerbate histological damage and motor deficits after experimental traumatic brain injury.
Angiotensin-converting enzyme (ACE) inhibitors are widely used as blood pressure medications in hypertensive individuals. However, ACE inhibitors also play an integral role in the breakdown of neuronal substance P, which has been recently implicated in the development of functional deficits following traumatic brain injury (TBI). The present study therefore examined the effects of ACE inhibitors on histological and motor outcome following TBI. Male Sprague-Dawley rats were treated with Captopril, Enalapril or equal volume saline for 7 days prior to the induction of diffuse TBI using the impact acceleration model. At 5h post-injury, animals administered Captopril demonstrated significantly increased substance P immunoreactivity compared to vehicle controls (p<0.01), and increased dark cell change that persisted to 7 days post-trauma. Captopril also resulted in exacerbated motor deficits compared to vehicle treated animals (p<0.05) as assessed by the rotarod test over a 7-day post-traumatic period. Administration of the alternative ACE inhibitor, Enalapril, likewise exacerbated motor deficits, confirming a class effect of ACE inhibitors rather than a compound effect specific to Captopril. We conclude that ACE inhibitors are deleterious to outcome following TBI, presumably by impairing the degradation of substance P and increasing substance P mediated neuronal injury.
Harford-Wright
Elizabeth
E
Discipline of Anatomy and Pathology, School of Medical Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
Thornton
Emma
E
Vink
Robert
R
D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications*; D002216:Captopril / Q000009:adverse effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004656:Enalapril / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D045442:Rotarod Performance Test / Q000379:methods; D013373:Substance P / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D013373:Substance P; D004656:Enalapril; D002216:Captopril