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Mitochondrial N‐formyl peptides cause hypotension via formyl peptide receptor activation (1157.6)
Author(s) -
Wenceslau Camilla
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1157.6
Subject(s) - vasodilation , sepsis , medicine , antagonist , receptor , endocrinology , chemistry , basal (medicine) , pharmacology , insulin
Hypotension is the major pathophysiological characteristic of systemic inflammatory response syndrome (SIRS) and sepsis. Mitochondrial N‐formyl peptides (F‐MIT) are a damage‐associated molecular pattern that activate the innate immune system via the formyl peptide receptor (FPR). We hypothesized that F‐MIT activates FPR and induces hypotension. Male Wistar rats (12‐weeks old) were cannulated (femoral artery and vein) for blood pressure recordings and drug infusion. F‐MIT infusion (0.02 or 0.2 mg/rat) decreased blood pressure (Low dose: Basal: 82±3 vs. F‐MIT infusion: 60±4*mmHg; High Dose: Basal: 79±3 vs. F‐MIT infusion: 41±3*mmHg;*p<0.05). WRW4 (FPR‐2 antagonist: 0.2 mg/rat), L‐NAME (NOS inhibitor: 15 mg/rat) and ODQ (guanylate cyclase (GC) inhibitor: 0.6 mg/rat) all abolished F‐MIT‐induced hypotension and cyclosporine H (FPR‐1 antagonist: CsH, 3 mg/rat) partially reduced this response. Also, isolated mesenteric resistance arteries were used to assess F‐MIT on vascular function. F‐MIT (10‐30 μM) induced relaxation (~30%) but ODQ or WRW4 abolished this response. However, L‐NAME (100 μM) or CsH (1 μM) only partially inhibited the vasodilatation. These data suggest that FPR‐2>FPR‐1 activation induces hypotension via NO. However, the vasodilatation induced by FPR‐2 is mediated by mechanisms that are NO‐independent but GC‐dependent. Thus, F‐MIT may be a link between trauma, sterile SIRS and sepsis. Grant Funding Source : Supported by NIH, CNPq and AHA