A role for abdominal vagal afferents in lipopolysaccharide-induced hypotension.
Lipopolysaccharide (LPS) mimics many of the effects of septic shock, including hypotension. LPS-induced hypotension has been attributed to nitric oxide (NO) activation of leukocytes, oxidants, cytokines, and other causes. However, there are some observations inconsistent with these "biochemical" causes. This study investigated a "physiological" mechanism: Are abdominal vagal afferent neurons involved in LPS-induced hypotension? The involvement of NO and leukocytes was also considered. Intravenous LPS (5 mg/kg) was used to induce hypotension in anesthetized rats. Subdiaphragmatic vagal activity was blocked with perivagal lidocaine (2%). Intravenous capsaicin (CAP, 1 mg/kg) or resiniferatoxin (RTX, 1 microg/kg) were used to inhibit afferent neural activity about 30 min before LPS. CAP and RTX have different receptors on different afferent nerves. Blood pressure, plasma nitrate and nitrite (NOx), stable products of NO, and leukocytes were measured over 3 h. LPS-induced hypotension was markedly attenuated by perivagal lidocaine and i.v. RTX, but was not affected by i.v. CAP. LPS caused a marked, transient decrease in leukocytes, mainly neutrophils, which was over within 10 min. This early leukocyte response was not affected by treatments that reduced LPS-induced hypotension. NO increased 3 h after LPS, and the changes in NO were not associated with effects of the pretreatments on blood pressure. It was concluded that abdominal vagal afferents are early mediators of LPS-induced hypotension. Also, NO and leukocytes were not direct mediators of the hypotension.
Mailman
David
D
Department of Biology and Biochemistry, University of Houston, Texas 77204, USA.
D000818:Animals; D001795:Blood Pressure Determination; D002211:Capsaicin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D007022:Hypotension / Q000209:etiology* / Q000503:physiopathology; D007275:Injections, Intravenous; D007958:Leukocyte Count; D008012:Lidocaine / Q000494:pharmacology*; D008070:Lipopolysaccharides; D009407:Nerve Block; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity; D012772:Shock, Septic / Q000209:etiology* / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology*
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D008012:Lidocaine; D019001:Nitric Oxide Synthase; D002211:Capsaicin