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.