DIFFERENTIAL INTESTINAL MICROVASCULAR DYSFUNCTION OCCURS DURING BACTEREMIA

Altered vascular responsiveness is the hallmark of septic shock. Recen tly, these changes have frequently been attributed to increased produc tion of nitric oxide (NO). Continued exposure to high levels of NO may alter both endothelial and vascular smooth muscle cell function. Alth ough ex vivo studies demonstrate hyporeactivity of large conduit arter ies during established sepsis, it is unclear if the same phenomena exi st during early sepsis. This is especially true in the small resistanc e arterioles of the viscera. We used in vivo microscopy of the rat sma ll intestine to assess (1) endothelial-dependent relaxation and vasomo tion (periodic contraction and relaxation of blood vessels) in respons e to acetylcholine (ACH; 10(-8) to 10(-5) M), (2) endothelial-independ ent relaxation to nitroprusside (NTP; 10(-5) M), and (3) vascular smoo th muscle response to norepinephrine (NE; 10(-10) to 10(-7) M) in norm al and bacteremic rats (Escherichia coli). There were no alterations i n endothelial-dependent or -independent relaxation during bacteremia a s measured by mean diameters. However, acute E. coli bacteremia severe ly 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 re sponse to NE was impaired, while A3 were minimally altered despite bei ng more sensitive to E. coli-induced vasoconstriction. These data sugg est that bacteremia causes a rapid, differential impairment of both en dothelial-dependent (A3 vasomotion) and vascular smooth muscle cell (A 1 constriction) functions. These microvascular impairments occur much earlier than previously described and may contribute to sepsis-induced mucosal ischemia of the intestines. (C) 1997 Academic Press.