The role of endothelin in the cerebrovascular response following intracerebral haemorrhage: experimental studies using the endothelin antagonist SB209670.
Primary intracerebral haemorrhage (ICH) is associated with considerable morbidity and mortality. Local endothelin release following ICH may contribute to the pathophysiology of perilesional ischaemia. In diabetics, endothelin release can be enhanced by hyperglycaemia and cerebrovascular dilation may be inhibited by vascular endothelial dysfunction. To examine the effects of endothelin-mediated vasoconstriction after spontaneous ICH in the normal and diabetic brain, regional cerebral blood flow (rCBF) was examined in insulin dependent BB-rats and non-diabetic BB control rats. These experiments were performed 24 h following experimental ICH in both groups of animals that were either given the endothelin antagonist SB209670 or saline. Perilesional oligaemia was similar in control and SB209670 treated diabetic rats, but SB209670 reduced perilesional oligaemia in normal rats. In brain contralateral to the experimental ICH, rCBF was increased by SB209670 in diabetic rats, but not in non-diabetic rats. These studies show that there are differences in the cerebrovascular effects of endothelin in perilesional and contralateral brain in non-diabetic and diabetic rats following ICH.
Fouyas
I P
IP
Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Brennan
P
P
Kelly
P A T
PA
Whittle
I R
IR
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D003921:Diabetes Mellitus, Experimental; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D006406:Hematoma / Q000378:metabolism* / Q000473:pathology; D007189:Indans / Q000008:administration & dosage*; D051381:Rats; D011913:Rats, Inbred BB
D002317:Cardiovascular Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D007189:Indans; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-