Vascular smooth muscle function: The physiology and pathology of vasoconstriction  Joseph F. Clark, Gail Pyne-Geithman  Pathophysiology  Volume 12, Issue 1, Pages 35-45 (July 2005) DOI: 10.1016/j.pathophys.2005.02.007 Copyright © 2005 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Physiological contractile mechanisms in smooth muscle. This figure illustrates the pathways involved in physiological contractile and relaxation responses in vascular smooth muscle, such as cerebral artery. Perturbations of many of these pathways have been examined as putative etiology of various vascular pathologies, including hypertension and cerebral vasospasm after subarachnoid hemorrhage. There are likely many other pathways not yet implicated, or indeed discovered, but this is the current state of knowledge. Below is the key for the figure. A, actin; Ag, agonist; AM, actomyosin; ATP/ADP, adenosine tri/diphosphate; BOXes, bilirubin oxidation products; Ca2+, calcium; Ca2+V,voltage gated calcium channels; CaCaMK, calcium calmodulin kinase; CaD, caldesmon; CaM, calmodulin; CPI-17 (a/i), MLCP inhibitory protein (active/inactive); CSFV, cerebrospinal fluid from SAH patients with cerebral vasospasm; DAG, diacyl glycerol; K+, potassium; IP3, inositol-3-phosphate; M, myosin; MAPK, mitogen-activated protein kinase; MLCK (a/i), myosin light chain kinase (active/inactive); MLCP, myosin light chain phosphatase; p, phosphate; PA, phosphatidic acid; PC, phosphatidyl choline; PIP2, phosphatidylinositol-2-phosphate; PKC, protein kinase C; PLC, phospholipase C; PLD, phospholipase D; R, receptor; Rho A (a/i), Rho A (active/inactive); ROK, Rho kinase; SR, sarcoplasmic reticulum; +/Ø, activates/inhibits. Pathophysiology 2005 12, 35-45DOI: (10.1016/j.pathophys.2005.02.007) Copyright © 2005 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 Bilirubin is a conjugated bond system with four pyrroles. When bilirubin is oxidized by hydrogen peroxide or other reactive oxygen species it is sometime cleaved at the nitrogen group of one of the middle pyrroles. This results in two bilirubin oxidation products, which are isomers. One isomeric form differs by the location of the methyl and vinyl groups of the original bilirubin pyrroles. Both BOX isoforms have been identified in the CSF, thus the mixture of the two BOX compounds is referred to as BOXes. Pathophysiology 2005 12, 35-45DOI: (10.1016/j.pathophys.2005.02.007) Copyright © 2005 Elsevier Ireland Ltd Terms and Conditions