Sepsis is the leading cause of mortality in critically ill patients. In this pathological syndrome, septic shock and sequential multiple organ failure correlate with poor outcome. The pathophysiology of sepsis with acute organ dysfunction involves a highly complex, integrated response that includes activation of number of cell types, inflammatory mediators, and the hemostatic system. Central to this process may be alterations in vascular functions. This review article provides a growing body of evidence for the potential impact of vascular dysfunction on sepsis pathophysiology with a major emphasis on the endothelium. Furthermore, the role of apoptotic signaling molecules in the mechanisms underlying endothelial cell injury and death during sepsis and its potential value as a target for sepsis therapy will be discussed, which may help in the assessment of ongoing therapeutic strategies.

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To determine an in vivo venodilatation of nasal mucosa, which is thought to be one of the causes of nasal obstruction in allergic rhinitis, venous diameters of nasal septa were directly measured in anesthetized rats. An application of antigen to nasal mucosa of sensitized rats caused an increase in diameters of mucosal veins, that is, venodilatation: the maximal response (about 20% increase in diameters) was observed at 55 min after antigen challenge. The antigen-induced increase in venous diameter of nasal mucosa was significantly inhibited by pretreatment with a cysteinyl leukotrienes (CysLTs) receptor antagonist, SR2640, and a nitric oxide (NO) synthase inhibitor, N^G-monomethyl-L-arginine, indicating that CysLTs and NO might be involved in the venodilatation of nasal mucosa induced by antigen challenge. Blocking the action of CysLTs and NO might be therefore useful for the therapy of nasal obstruction in allergic rhinitis.

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The effects of strepozotocin (STZ)-induced diabetes on the spontaneous peristaltic contractions in the upper urinary tract (UUT) of the rat were examined by simultaneously recording the tension in the proximal and distal regions of the renal pelvis and the proximal ureter. All regions of the UUT of diabetic rats contracted at a frequency similar to the contraction frequency of age-matched control rats. In contrast, contraction amplitudes in the proximal and distal renal pelvis and ureter of diabetic rats were 36%, 135% and 121% larger than the equivalent contractions recorded in control rats resulting in a significant increases in the motility index (MI amplitude x frequency) in all 3 regions. Capsaicin (10 μM), substance P (SP 2 μM) and neurokinin A (NKA 2 μM) caused a transient increase in MI in both control and STZ-induced diabetic rats. The rise in basal tension in the proximal and distal renal pelvis evoked by capsaicin, SP or NKA was also significantly greater in the diabetic rats when compared with controls. In contrast, human calcitonin-gene related peptide (hCGRP) produced a relatively small transient inhibition of UUT motility which was little affected by STZ treatment. These results suggest that capsaicin predominantly releases tachykinins from intrinsic sensory nerves in both non-diabetic and STZ-induced diabetic rats. We speculate that the supersensitivity of the diabetic UUT to capsaicin, NKA and SP 8-10 weeks after STZ treatment could be arising from an earlier development of sensory neuropathy.

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