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.
Rafols
D
D
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Steiner
J
J
Rafols
J A
JA
Petrov
T
T
D000818:Animals; D001930:Brain Injuries / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D019332:Endothelin-1 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D007424:Intracellular Fluid / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
D019332:Endothelin-1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat