Effects of Pseudomonas aeruginosa endotoxin on vasodilation in the intact spinotrapezius muscle

The purpose of this study was to determine whether short-term exposure to c linically relevant concentrations of Pseudomonas aeruginosa lipopolysacchar ide (LPS) impairs vasoreactivity of resistance arterioles in the intact spi notrapezius muscle microcirculation and, if so, to determine the mechanisms mediating this response. Using intravital microscopy, we found that 60-min suffusion of P. aeruginosa LPS (0.03-3.0 mug/ml) on the in situ hamster sp inotrapezius muscle elicited an immediate, profound, and prolonged concentr ation-dependent vasodilation (P < 0.05). This response was reversible once suffusion of P. aeruginosa LPS was stopped. Pretreatment with N-G-nitro-L-a rginine methyl ester (10.0 <mu>M), a nonselective nitric oxide (NO) synthas e inhibitor, but not N-G-nitro-D-arginine methyl ester, abrogated P. aerugi nosa LPS-induced vasodilation and elicited a small, albeit significant, vas oconstriction. Indomethacin had no significant effects on P. aeruginosa LPS -induced responses. P. aeruginosa LPS had no significant effects on acetylc holine- and nitroglycerin-induced vasodilation in the spinotrapezius muscle . Collectively, these data indicate that short-term exposure to clinically relevant concentrations of P. aeruginosa LPS evokes an immediate, potent, p rolonged, and reversible NO-dependent, prostaglandin-independent vasodilati on in skeletal muscles in vivo. We suggest this response could play an impo rtant role in the pathophysiology of the profound vasomotor dysfunction obs erved in the peripheral circulation of patients with P. aeruginosa sepsis s yndrome.