200 PART I Basic Science macromolecular leakage can be made simultaneously; and (3) monitored superfusion of the HCP facilitates mediator administration and drug treatment with great accuracy. Bibliography Granger, D. N., and Kubes, P. (1994). The microcirculation and inflamma- tion: Modulation of leukocyte-endothelial cell adhesion. J. Leukocyte Biol. 55, 662–675. A comprehensive description and guide for the understanding of leukocyte–endothelial interactions that is still useful although it was published in 1994. Korthuis, R. J., Dayton, C., and Yamaguchi, T. (2003). Early and late pre- conditioning prevents ischemia/reperfusion injury: Signaling pathways mediating the adaptive metamorphosis to a protective phenotype in pre- conditioned tissues. In Molecular Basis for Microcirculatory Disorders (G. W. Schmid-Schönbein and D. N. Granger, eds.), pp. 343–363. France, Paris: Springer-Verlag. This review is very useful for the under- standing of the phenomenon of preconditioning, an important protec- tive mechanism in inflammation. Ley, K., and Sperandio, M. (2003). Molecular mechanisms of leukocyte adhesion. In Molecular Basis for Microcirculatory Disorders (G. W. Schmid-Schönbein and D. N. Granger, eds.), pp. 1–71. France, Paris: Springer-Verlag. A very complete review covering all aspects of leuko- cyte rolling, firm adhesion, and transmigration, and also details of mechanisms of adhesive proteins with references to more than 400 publications. McDonald, D. M., Thurston, G., and Baluk, P. (1999). Endothelial gaps as sites for plasma leakage in inflammation. Microcirculation 6, 7–22. Persson, C. G. A., and Svensjö, E. (1985). Vascular responses and their sup- pression: Drugs interfering with venular permeability. In Handbook of Inflammation (I. L. Bonta, M. A. Bray, and M. J. Parnham, eds.), Vol. 5, The Pharmacology of Inflammation, pp. 61–82. Amsterdam, Netherlands: Elsevier. Describes the basis for the concept of the endothelial cells in the postcapillary venules as the site for physiologi- cal and pharmacological regulation of vascular permeability increase in inflammation. Capsule Biography Dr. Svensjö has worked as senior pharmacologist at two major pharma- ceutical companies in Sweden and is now at Laboratorio Imunologia Mol- ecular, Instituto Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro. The laboratory focuses on mechanisms of parasite infection (Trypanosoma cruzi, leishmaniasis). The lab is supported by grants from FAPERJ, CNPq, and WHO. SECTION D Permeability, Tone and Hemodynamics [...]... stores, PKC 2-APB, Ni2+, Cd2+, Gd3+, La3+ SAC TRPC 6 or TRPM4 ? ? 25 30 Membrane stretch, PKC G spatulata venom, SKF 9 636 5, amiloride, Gd3+, La3+ ROC TRPC 6? ? ? 25 30 DAG, PKC? SKF 9 636 5, amiloride, Gd3, La3+ BKCa Slo1 — or ? Slo b 250 Depolarization, ≠[Ca2+]in, NO, CO, EETs Iberiotoxin, charybdotoxin, penitrem A, paxillin, 1 mM TEA sKCa — or ? SK3 Calmodulin 4–20 ≠[Ca2+]in Apamin, d-tubocurarine,... acid; 9-AC, 9-anthracenecarboxylic acid; NPPB, 5-nitro- 2-( 3- phenylpropylamino)benzoic acid e —, Not present; ?, present, but specific isoform unclear, or mechanism unclear b nifedipine, activate at very negative membrane potentials (-7 0 mV), and inactivate rapidly, and nifedipine-insensitive, high voltage-activated Ca2+ channels (R-type Ca2+) with activation properties similar to those of L-type channels... treatment from the molecular and structural biology of K+ channels to their function and pharmacology Recommended reading for anyone interested in K+ channels and the cardiovascular system Beech, D J., Xu, S Z., McHugh, D., and Flemming, R (20 03) TRPC1 store-operated cationic channel subunit Cell Calcium 33 (5–6), 433 –440 Busse, R., Edwards, G., Feletou, M., Fleming, I., Vanhoutte, P M., and Weston, A H (2002)... phospholipase C-b (PLC-b) leading to the formation of inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG, not shown) 2, IP3 binds to IP3-receptors (IP3R) on the smooth endoplasmic reticulum, releasing stored Ca2+ 3, This causes a rapid rise in intracellular Ca2+ 4, The increased [Ca2+]in then binds to calmodulin (CAM) associated with a number of proteins including intermediate (IKCa) and small (sKCa)... arterial smooth muscle by acetylcholine Nature 288, 37 3 37 6 Davidge, S T (2001) Prostaglandin H synthase and vascular function Circ Res 89, 650–660 Fleming, I., and Busse, R (2000) Activation of NOS by Ca2+-dependent and Ca2+–independent mechanisms In Nitric Oxide (L J Ignarro, ed.), San Diego: Academic Press, pp 621– 632 Fleming, I., and Busse, R (20 03) Molecular mechanisms involved in the regulation... dissociation from caveolin and increases NO production Shear stress–induced increases in endothelial NO production can be abrogated by preventing the activation of PI 3- K (C) (see color insert) CHAPTER 33 Autacoid Production by Hemodynamic Forces example, in wild-type mice flow-dependent vasodilatation in gracilis muscle arterioles appears to be mediated by NO However, in male eNOS- /- mice, flow-induced vasodilatation... the so-called resistance vessels, that is, small terminal arteries and large and small arterioles Endothelial cells, situated at the interface between blood and the vessel wall, play a crucial role in controlling vascular tone and homeostasis, particularly in determining the expression of pro- and antiinflammatory genes Many of these effects are mediated by the generation and release of endothelium-derived... and arrows indicate stimulatory effects, whereas dashed lines represent inhibitory effects 1, Vasoconstrictors such as norepinephrine, angiotensin II, vasopressin or endothelin, bind to G-protein-coupled receptors to activate effector proteins such as phospholipase C-b (PLC-b) 2, Activated PLC-b then acts on membrane phospholipids to form inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) 3, ... voltage-gated K+ channels (KV), and large-conductance Ca2+-activated K+ channels (BKCa) 5, In addition to activating PKC, DAG also can activate receptor-operated channels (ROC) 6, The release of Ca2+ from intracellular stores, through, or in addition to, activation by PKC, opens SOC channels 7, The influx of Ca2+ and Na+ through SAC, SOC, and ROC, along with Cl- efflux through Ca2+-activated Cl- channels... potential and tone, participate in functional hyperemia, and mediate, in part, hypoxia-induced vasodilation in these tissues KIR CHANNELS Arteriolar smooth muscle and endothelial cells also express KIR channels These channels open with small, physiological increases in extracellular K+ concentration (Figure 3) and may participate in functional hyperemia in skeletal muscle, cardiac muscle, and the brain . Physiol. 38 8, 421– 435 . Bibliography Adamson, R. H., and Michel, C. C. (19 93) . Pathways through the intercel- lular clefts of frog mesenteric capillaries. J. Physiol. (Lond.) 466, 30 3 32 7. The first, and. phenotype in pre- conditioned tissues. In Molecular Basis for Microcirculatory Disorders (G. W. Schmid-Schönbein and D. N. Granger, eds.), pp. 34 3 36 3. France, Paris: Springer-Verlag. This review. to 3mm and usually 50 to 200nmlong and overlapping junc- tional strands further into or out of the cleft, give rise to a Copyright © 2006, Elsevier Science (USA). 2 03 All rights reserved. 204 PART