VASCULAR SMOOTH MUSCLE SIGNALS UPREGULATE ENDOTHELIAL CYCLOOXYGENASE EXPRESSION IN THE NEWBORN PIG CEREBRAL CIRCULATION. † 1403

Abstract

Cellular communication between vascular endothelium and smooth muscle are important in the regulation of vascular function. In the newborn cerebral circulation, endothelium-derived cyclooxygenase products participate in vascular smooth muscle responsiveness to many physiological stimuli. Our present data indicate that vascular smooth muscle, in turn, may influence functions of vascular endothelium. Endothelial cells from the newborn pig cerebral microvessels cultured separately or in coculture with microvascular smooth muscle cells were used to investigate a possible role of cellular communication in the regulation of endothelial cyclooxygenase expression. Microvascular endothelial cells (freshly isolated as well as confluent and quiescent primary cultures) constitutively express both cyclooxygenase isoforms, COX-1 and COX-2, as detected by Western blots and immunostaining with the isozyme-specific antibodies. Results with the isozyme-selective inhibitor NS-398 suggest that COX-2 provides a large portion of endothelial prostanoid production. Endothelial cells grown in non-contact coculture with smooth muscle cells for 24-48 hr show induction of COX-1 and COX-2 proteins. There are a 10-50-fold increases in endogenous prostanoid accumulation and cyclooxygenase activity that are inhibited by dexamethasone, cycloheximide and actinomycin D. Similar changes are induced in endothelial cells exposed to smooth muscle cell-conditioned media. These results indicate that cerebral microvascular smooth muscle cells produce a diffusable compound(s) that upregulate endothelial cyclooxygenase thus modifying endothelial cell function.