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

Abstract

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.