Intraventricular endothelin-1 uncouples the blood flow: metabolism relationship in periventricular structures of the rat brain: involvement of L-type calcium channels.
Endothelin-1 (ET) produces contraction of cerebral resistance vessels in vitro and in situ, but also is neuroactive causing increases in tissue energy metabolism as measured by [14C]deoxyglucose autoradiography in the intact rat brain. ET may, therefore, disengage the normally tight linkage between cerebral blood flow and tissue metabolism. Using anatomically rigorous autoradiographic and imaging techniques to measure focal blood flow in anesthetized, ventilated rats, we found that intraventricular injection of 9 pmol of ET reduced rates of perfusion by an average of 29% (compared to a saline-injected condition) in 6 individual periventricular structures bordering the injected lateral ventricle. A significant vasoconstrictor effect (41% decrease in blood flow) also occurred in the ipsilateral choroid plexus after ET injection, despite its increased rate of glucose metabolism. We employed a hydrogen clearance method to monitor rates of blood flow serially within the periventricular margin of the caudate nucleus after intraventricular injection of the dihydropyridine calcium-channel antagonist, nimodipine (72 nmol), or 9 pmol ET, alone and in sequence. Nimodipine increased caudate blood flow (by 47%) and prevented the vasoconstriction produced by ET. The results indicate that ET causes vasoconstriction in penventricular brain structures and choroid plexus even in the presence of substantial increases in glucose metabolism. The simultaneous stimulation by intraventricular ET of tissue hypermetabolic and vascular constrictor mechanisms, leading to a net reduction of periventricular blood flow, is mediated, at least in part, by dihydropyridine-sensitive calcium L-channels.
Gross
P M
PM
Department of Surgery, Queen's University, Kingston, Ontario, Canada.
Zochodne
D W
DW
Wainman
D S
DS
Ho
L T
LT
Espinosa
F J
FJ
Weaver
D F
DF
D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002421:Caudate Nucleus / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003847:Deoxyglucose / Q000378:metabolism; D016232:Endothelins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D015220:Calcium Channels; D016232:Endothelins; D009553:Nimodipine; D003847:Deoxyglucose