ABSTRACT
EDHF-mediated dilatations were studied in the rat middle cerebral artery following ischemia/reperfusion. The ischemia/reperfusion model consisted of 2 hours of unilateral focal ischemia followed by 24 hours of reperfusion. Controls or sham-injured rats underwent brief vessel occlusion followed by 24 hours of reperfusion. Following the ischemia/reperfusion or sham-injury protocols, middle cerebral arteries were isolated, pressurized to 85 mmHg, and luminally perfused. EDHF-mediated responses were evaluated using luminal applications of uridine triphosphate (UTP), a P 2 Y 2 selective agonist, or A23187, a C a 2 + ionophore, following the inhibition of nitric oxide synthase. Middle cerebral arteries from both sham and ischemia/reperfusion rats dilated max imally to the luminal application of U T P or A23187 in the presence of N^-nitroL-arginine methyl ester ( L - N A M E , 10~5 M ) . However, U T P was seven times more potent and A23187 was three times more potent in middle cerebral arteries from ischemia/reperfusion rats compared to shams. Indomethacin (10~ 5 M), an inhibitor of cyclooxygenase, did not alter the L - N A M E insensitive component of the UTP-mediated dilatation in reperfused arteries. In the presence of L - N A M E , dilatations to U T P were accompanied by smooth muscle hyperpolarization. Dilatations to U T P and A23187 in the presence of L - N A M E were blocked by charybdotoxin (10~7 M ) , an inhibitor of the calcium activated potassium channels. Thus, ischemia/reperfusion potentiates EDHF-mediated dilatations in the rat middle cerebral artery. The upregulation of the EDHF-mediated response may offer cerebral protection during pathological conditions.
