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TRPV1-mediated protection against endotoxin-induced hypotension and mortality in rats Wang Y; Novotny M; Quaiserova-Mocko V; Swain GM; Wang DHAm J Physiol Regul Integr Comp Physiol 2008[May]; 294 (5): R1517-23This study was designed to test the hypothesis that the transient receptor potential vanilloid type 1 (TRPV1) channel, expressed primarily in sensory nerves, and substance P (SP), released by sensory nerves, play a protective role against lipopolysaccharide (LPS)-induced hypotension. LPS (10 mg/kg iv) elicited tachycardia and hypotension in anesthetized male Wistar rats, which peaked at 10 min and gradually recovered 1 h after the injection. Blockade of TRPV1 with its selective antagonist capsazepine (CAPZ, 3 mg/kg iv) impaired recovery given that the fall in mean arterial pressure (MAP) was greater 1 h after CAPZ plus LPS injections compared with LPS injection alone (45 +/- 5 vs. 25 +/- 4 mmHg, P < 0.05). Blockade of the neurokinin 1 (NK1) receptor with its selective antagonists RP-67580 (5 mg/kg iv) or L-733,060 (4 mg/kg iv) prevented recovery, considering that falls in MAP were not different 1 h after injections of NK1 antagonists plus LPS from their peak decreases (66 +/- 9 vs. 74 +/- 5 mmHg or 60 +/- 7 vs. 69 +/- 3 mmHg, respectively, P > 0.05). LPS increased plasma SP, norepinephrine (NE), and epinephrine (Epi) levels compared with vehicles, and the increases in plasma SP, NE, and Epi were significantly inhibited by CAPZ or RP-67580. The survival rate at 24 or 48 h after LPS injection (20 mg/kg ip) was lower in conscious rats pretreated with CAPZ or RP-67580 compared with rats treated with LPS alone (P < 0.05). Thus our results show that the TRPV1, possibly via triggering release of SP which activates the NK1 and stimulates the sympathetic axis, plays a protective role against endotoxin-induced hypotension and mortality, suggesting that TRPV1 receptors are essential in protecting vital organ perfusion and survival during the endotoxic condition.|Animals[MESH]|Blood Pressure/drug effects[MESH]|Capsaicin/analogs & derivatives/pharmacology[MESH]|Catecholamines/blood[MESH]|Endotoxins/*toxicity[MESH]|Heart Rate/drug effects[MESH]|Hypotension/*chemically induced/mortality/*prevention & control[MESH]|Isoindoles/pharmacology[MESH]|Lipopolysaccharides/toxicity[MESH]|Male[MESH]|Neurons, Afferent/drug effects[MESH]|Rats[MESH]|Rats, Wistar[MESH]|Receptors, Neurokinin-1/physiology[MESH]|Substance P/metabolism[MESH]|TRPV Cation Channels/*physiology[MESH] |
