Acute cocaine alters cerebrovascular autoregulation in the rat neocortex.
Although cocaine abuse has been associated with an increased incidence of cerebrovascular accident, the underlying mechanisms are unknown. In this study we have investigated the effects of cocaine upon the autoregulation of local cortical blood flow (lCBF) during hypertension. Hypertension was induced in conscious rats by intravenous infusion of angiotensin-II (5 micrograms/ml; 0.5-2.5 ml/h), and animals were subsequently injected IV with either cocaine-HCl (5 mg/kg) or saline, prior to the measurement of lCBF of glucose utilization (lCGU) using [14C]-iodoantipyrine or [14C]-2-deoxyglucose quantitative autoradiography, respectively. Hypertension alone (< 155 mmHg) did not significantly alter lCBF in any cortical areas examined. However, at higher mean arterial blood pressure (MABP), lCBF increased focally (+265%) in parietal cortex. Cocaine did not alter lCBF in normotensive animals, but with increasing levels of hypertension (MABP > 145 mmHg), all cocaine-treated rats showed focal increases (200-400%) in lCBF in parietal cortex. Glucose use remained relatively unaffected in all treatment groups. This hyperaemia in cocaine-treated rats at MABP below the normal upper limit of autoregulation may provide a mechanism to explain haemorrhagic stroke in cocaine abusers.
Department of Clinical Neurosciences, University of Edinburgh, UK.
P A
PA
Kelley
J
J
Sharkey
R
R
Philip
I M
IM
Ritchie
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D006940:Hyperemia / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000804:Angiotensin II; D003042:Cocaine; D005947:Glucose