Lipopolysaccharide induces relaxation in lung pericytes by an iNOS-independent mechanism

Lipopolysaccharide (LPS)-regulated contractility in pericytes may play an i mportant role in mediating pulmonary microvascular fluid hemodynamics durin g inflammation and sepsis. LPS has been shown to regulate inducible nitric oxide (NO) synthase (iNOS) in various cell types, leading to NO generation, which is associated with vasodilatation. The purpose of this study was to test the hypothesis that LPS can regulate relaxation in lung pericytes and to determine whether this relaxation is mediated through the iNOS pathway. As predicted, LPS stimulated NO synthesis and reduced basal tension by 49% (P < 0.001). However, the NO synthase inhibitors N-omega-nitro-L-arginine m ethyl ester, aminoguanidine, and N-omega-monomethyl-L-arginine did not bloc k the relaxation produced by LPS. In fact, aminoguanidine and N-omega-monom ethyl-L-arginine potentiated the LPS response. The possibility that NO migh t mediate either contraction or relaxation of the pericyte was further inve stigated through the use of NO donor compounds; however, neither sodium nit roprusside nor S-nitroso-N-acetylpenicillamine had any significant effect o n pericyte contraction. The inhibitory effect of aminoguanidine on LPS-stim ulated NO production was confirmed. This ability of LPS to inhibit contract ility independent of iNOS was also demonstrated in lung pericytes derived f rom iNOS-deficient mice. This suggests the presence of an iNOS-independent but as yet undetermined pathway by which lung pericyte contractility is reg ulated.