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Abstract
Altered vascular responsiveness is the hallmark of septic shock. Recently, these changes have frequently been attributed to increased production of nitric oxide (NO). Continued exposure to high levels of NO may alter both endothelial and vascular smooth muscle cell function. Although ex vivo studies demonstrate hyporeactivity of large conduit arteries during established sepsis, it is unclear if the same phenomena exist during early sepsis. This is especially true in the small resistance arterioles of the viscera. We used in vivo microscopy of the rat small intestine to assess (1) endothelial-dependent relaxation and vasomotion (periodic contraction and relaxation of blood vessels) in response to acetylcholine (ACH; 10(-8) to 10(-5) M), (2) endothelial-independent relaxation to nitroprusside (NTP; 10(-5) M), and (3) vascular smooth muscle response to norepinephrine (NE; 10(-10) to 10(-7) M) in normal and bacteremic rats (Escherichia coli). There were no alterations in endothelial-dependent or -independent relaxation during bacteremia as measured by mean diameters. However, acute E. coli bacteremia severely impaired vasomotion in A1 (inflow) and A3 (premucosal) arterioles. Vasomotion was returned to baseline levels in A1 with low-dose ACH (10(-8) M) but only partially improved in A3 arterioles (P < 0.05). A1 response to NE was impaired, while A3 were minimally altered despite being more sensitive to E. coli-induced vasoconstriction. These data suggest that bacteremia causes a rapid, differential impairment of both endothelial-dependent (A3 vasomotion) and vascular smooth muscle cell (A1 constriction) functions. These microvascular impairments occur much earlier than previously described and may contribute to sepsis-induced mucosal ischemia of the intestines.
View details for Web of Science ID A1997WK04700013
View details for PubMedID 9070184