Intracellular coexpression of endothelin-1 and inducible nitric oxide synthase underlies hypoperfusion after traumatic brain injury in the rat.

We used Marmarou's rat model of traumatic brain injury to demonstrate colocalization of mRNAs for endothelin-1 (ET-1, a powerful vasoconstrictor) and inducible nitric oxide synthase (iNOS, generator of NO, a vasodilator) in individual cells that form the brain's microvascular wall. The results were confirmed with double immunocytochemistry. After trauma endothelial, smooth muscle cells and macrophages contributed to the abnormal synthesis of ET-1 and iNOS which may underlie a dysfunctional brain microcirculation. This is the first in vivo single cell demonstration of ET-1 and iNOS colocalization, suggesting reciprocal regulation of each other's expression both at the transcriptional and translational levels. The results further indicate that interaction between ET-1 and iNOS occurs at the cytosol and possibly the nuclear membranes, implicating mediation via endothelin receptors. Copyright 2004 Elsevier Ireland Ltd.