Transient potential vanilloid 1 (
TRPV1) receptor is an
ion channel receptor primarily localized on sensory nerves and activated by specific stimuli to initiate and amplify
pain and
inflammation, as typified by murine models of scald and
arthritis. Little is known of the role of TRPV1 in
sepsis, an infective disease associated with
inflammation. Through use of a sublethal murine model of
lipopolysaccharide-induced peritoneal
sepsis, we provide novel evidence that genetic deletion of TRPV1 leads to an enhanced onset of various pathological components of systemic
endotoxemia. Paired studies of TRPV1 knockout (KO) and wild-type mice demonstrate significantly enhanced
hypotension (56+/-2% vs. 38+/-6% decrease in blood pressure, n=12),
hypothermia (13+/-3% vs. 7+/-1% decrease in core temperature, n=6), and peritoneal exudate mediator levels (
TNF-alpha, 0.78+/-0.2 vs. 0.38+/-0.1 ng/ml;
nitrite, for NO, 35+/-10 vs. 15+/-3 microM; n=8) in TRPV1 KO mice, indicating loss of protective effect. Findings correlated with liver
edema and raised plasma levels of
aspartate aminotransferase in TRPV1 KO mice. These data suggest that TRPV1 may play an important regulatory role in
sepsis independent of the major sensory
neuropeptide substance P. The findings are relevant to developing strategies that increase the beneficial, and reduce the harmful, components of
sepsis to prevent and treat this often fatal condition.