Conducted vasoconstriction is reduced in a mouse model of sepsis.

The ability of an arteriole to conduct vasomotor responses along its length contributes to the control of organ perfusion. Sepsis, a systemic inflammatory response to infection, may compromise this control. We aimed to determine whether sepsis, induced by cecal ligation and perforation (CLP), reduces conducted vasoconstriction 24 h post-CLP. We locally stimulated mouse cremaster arterioles with KCl, measured the resulting local and the conducted constriction (500 microm upstream) and, based on these measurements, determined the communication ratio (CR(500)) as an index of the conducted response. Sepsis significantly reduced the CR(500) from 0.75 to 0.20. Based on a mathematical model, this reduction was predicted to have a significant impact on blood flow control. In septic mice, either a 1-hour washout of the cremaster muscle with physiological saline or a treatment of this muscle with the tyrosine kinase inhibitor PP-2 (100 nM) restored the CR(500) to the control level. Treatment of septic arterioles with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (100 microM) partially restored the CR(500) from 0.2 to 0.4. In control mice, lipopolysaccharide (LPS; 10 microg/ml) superfused over the cremaster muscle for 1 h reduced the CR(500); the nitric oxide (NO) donor S-nitroso-N-acetyl-penicillamine (50 microM) also reduced the CR(500). Thus, LPS and NO could be two factors mediating reduced conduction of vasoconstriction in sepsis. We conclude that sepsis reduces the KCl-induced conducted vasoconstriction in the mouse cremaster muscle by a tyrosine kinase- and nitric oxide- dependent mechanism.