Effects of lschemia on Expression of Cyclooxygenase and Endothelial Nitric Oxide Synthase in the Cerebral Circulation

Summary

Ischemia/reperfusion (I/R) has many effects on the cerebral circulation including alterations in expression of enzymes mediating synthesis of factors such as prostanoids (prostaglandins and thromboxane) and nitric oxide (NO), which affect blood flow. Studies were directed toward examining effects of I/R on expression of cyclooxygenase (COX; types 1 and 2) and endothelial nitric oxide synthase (eNOS) in cerebral arteries and arterioles. Following 10 min of global ischemia induced by increasing intracranial pressure with artificial cerebrospinal fluid, COX-2 mRNA in large cerebral arteries (middle cerebral artery, circle of Willis, basilar artery) started to increase within 30 min and peaked at 2 h. By 8 h levels of COX-2 protein had increased dramatically, especially in endothelium. Similar findings were present in intraparenchymal arteries. COX-1 mRNA and protein levels did not increase after I/R. In contrast to COX-2, eNOS protein levels did not increase in large cerebral arteries. However, eNOS protein levels increased in parenchymal blood vessels. Levels of bNOS did not increase and iNOS levels were minimal after I/R. Similar to large arteries, in choroid plexus COX-2 protein increases were pronounced, and eNOS increases were relatively modest. Associated with increased levels of COX-2 mRNA was translocation of the NF-кB transcription factor from the cytosol to the nucleus. The consequences of enhanced COX-2 and eNOS protein levels are unclear at this time but probably result from a competition between beneficial and harmful effects.