1. A Close Look at the Endothelium: Its Role in the Regulation of Vasomotor Tone 
Manuel Mas 
European Urology Supplements 
Volume 8, Issue 2, Pages (January 2009)
DOI: /j.eursup
Copyright © 2008 European Association of Urology Terms and Conditions

2. Fig. 1
Electron microscopy image of a cross-section of a human capillary vessel of the continuous type showing some of the structural features discussed. Note the abundant cytoplasmic projections into the vessel lumen, sometimes contacting with an adjacent projection falsely resembling large intracellular vesicles; this is characteristic of highly activated endothelia such as those found in tumors (as in this case) or inflammatory states. These cytoplasmic projections eventually shed from the endothelial cells as circulating endothelial microparticles, regarded as markers of endothelial damage. Uranyl acetate and lead citrate (×18.000). Reprinted with permission from L. Diaz-Flores and R. Gutierrez (unpublished data, 2007).
BL=basal lamina; c=caveolae; icj=intercellular junctions (mainly of the adherens type); g=Golgi saccules; L=vessel lumen; m=mithocondria; N=nucleus.
European Urology Supplements 2009 8, 48-57DOI: ( /j.eursup )
Copyright © 2008 European Association of Urology Terms and Conditions

3. Fig. 2
Schematic drawing of the mechanism of endothelial nitric oxide synthase (eNOS) action (a) in normal circumstances and (b) in the “uncoupled” state resulting from tetrahydrobiopterine (BH4) deficiency and other forms of oxidative damage to the enzyme structure. The eNOS subunits are depicted in this fashion for the sake of clarity; in their actual conformation, the iron protoporphyrin IX (heme) groups (Fe) from the two subunits seem to lie in close proximity. In the normal state, BH4 molecules in conjunction with the heme groups hold both subunits tightly bound and keep the dimer stabilized. Thus, in the healthy endothelium, (a) electrons flow through the nicotinamide adenine dinucleotide phosphate (NADPH) and the flavin nucleotides (FAD, FMN) from the reductase domain of one subunit to the oxygenase domain in the other. Calmodulin (CaM) accelerates this process. BH4 is also critical for coupling the reduction of molecular oxygen (O2) at the heme group to the multistep oxidation of L-arginine yielding nitric oxide (NO) and L-citrulline. In the absence of BH4 (b), the electron flow from the reductase domain becomes uncoupled from l-arginine oxidation and eNOS generates superoxide (O2−) instead of NO.
European Urology Supplements 2009 8, 48-57DOI: ( /j.eursup )
Copyright © 2008 European Association of Urology Terms and Conditions

4. Fig. 3
Summary sketch of the metabolic pathways leading to the formation of the vasoactive derivatives of arachidonic acid, including the prostanoids, secreted by the endothelium. They all act through specific receptors in vascular smooth muscle cells (VSMCs). Depending on which enzymes become activated by different stimuli predominate the vasodilator (vd) or the vasoconstrictor (vc) prostanoids, although in normal circumstances the major metabolite is the vasodilator PGI2 (thick arrows). The enzymes are indicated in ovals.
EETs=epoxyeicosatrienoic acids.
European Urology Supplements 2009 8, 48-57DOI: ( /j.eursup )
Copyright © 2008 European Association of Urology Terms and Conditions

5. Fig. 4
Summary sketch of the complex role of reactive oxygen species (ROS) in endothelial cell (EC) biology. Depending on their generation rate, ROS can act either as physiologic regulatory signals or as mediators of EC dysfunction and other forms of vascular damage. Because of its relative stability and easy diffusion, hydrogen peroxide (H2O2) seems especially suited to act as an intercellular signal as well as an intracellular regulator of EC functions (eg, endothelial nitric oxide synthase [eNOS] activity).
ONOO−=peroxynitrite; BH4=tetrahydrobiopterine; Ca2+=calcium; VSMCs=vascular smooth muscle cells.
European Urology Supplements 2009 8, 48-57DOI: ( /j.eursup )
Copyright © 2008 European Association of Urology Terms and Conditions