The role of inducible nitric oxide synthase in lipopolysaccharide-mediated hyporeactivity to vasoconstrictors differs among isolated rat arteries

Abstract

We investigated whether organ-specific differences exist in the role of inducible nitric oxide synthase (iNOS) in hyporeactivity to vasoconstrictors following 20 h in vitro exposure of isolated superior mesenteric, renal, hepatic and coronary arteries from the rat to bacterial lipopolysaccharide (LPS). LPS attenuated contraction in response to depolarizing KCl in all arteries. Maximum contractile responses to noradrenaline were attenuated in superior mesenteric and hepatic arteries, and those to the thromboxane A(2) analogue U46619 were attenuated in coronary arteries. LPS shifted the concentration-response curve to noradrenaline in renal arteries to the right. Removal of extracellular L-arginine improved the response to noradrenaline in superior mesenteric and renal arteries only. Addition of the iNOS inhibitor aminoguanidine resulted in full recovery of the responses to noradrenaline in superior mesenteric, renal and hepatic arteries. Contractile responses in coronary arteries did not improve after inhibition of iNOS activity. Therefore the pattern of the LPS-induced changes in vascular reactivity, as well as the contribution of iNOS to impaired vascular constriction, differed among vascular beds. These differences are likely to represent a contributory factor in the sepsis-associated redistribution of cardiac output.

Renal transcription of high‐affinity type‐2 cationic amino acid transporter is up‐regulated in LPS‐stimulated rodents

“…As aforementioned, renal vasoconstriction and decreased GFR are two of the major mechanisms that lead to acute renal failure during sepsis (8)(9)(10). Previous reports indicated that endotoxemia-induced decreases in GFR would happen within hours after LPS exposure and would deteriorate even further if intervention was not installed (34)(35)(36).…”

“…Renal vasoconstriction and decreased glomerular filtration rate (GFR) are two of the major mechanisms that lead to acute renal failure during sepsis (8)(9)(10). Previous studies indicated that the decrease in GFR after sepsis is related to local inhibition of glomerular endothelial NOS (eNOS) by overproduced NO generated by sepsis-induced iNOS (10)(11)(12).…”

NO and KATP channels underlie endotoxin‐induced smooth muscle hyperpolarization in rat mesenteric resistance arteries

“…In addition to variability between experimental regimes, both the pattern of the LPS-induced changes in vascular reactivity and the contribution of inducible NO synthase to the impaired vascular constriction differ between vascular beds (Piepot et al, 2002). Thus, at the level of resistance arteries, it remains unclear how significant hyporeactivity is, and the mechanism(s) responsible.…”

Endotoxin Releases a Substance from the Aorta that Dilates an Isolated Arteriole by Up-Regulating INOS

“…The arteriole was exposed to buffer, L-NAME (100 M), or aminoguanidine (100 M), which was introduced in a side branch between the aortic segment and the arteriolar bath (Fig. 2) [11]. At t ϭ 60 min, segments of aorta and arteriole were superfused with 2.5 g/ml Salmonella enteritidis endotoxin (Sigma Chemical Co., St. Louis, MO) or Krebsbicarbonate-HEPES buffer solution for 60 min or t ϭ 120 min.…”