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Propofol and vascular regulation: Role of TRPA1 and TRPV1 ion‐channels
Author(s) -
Sinha Roy Pritam,
Sinha Sayantani,
Bratz Ian,
Damron Derek
Publication year - 2015
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.29.1_supplement.lb487
Subject(s) - propofol , trpv1 , transient receptor potential channel , chemistry , sevoflurane , pharmacology , in vivo , anesthetic , mean arterial pressure , nitric oxide , anesthesia , endocrinology , medicine , blood pressure , receptor , biochemistry , heart rate , biology , microbiology and biotechnology , organic chemistry
Background Transient receptor potential (TRP) ion channels of the A1 (TRPA1) and V1 (TRPV1) subtypes are key regulators of vasomotor tone. Propofol, an intravenous anesthetic known to cause vasorelaxation. Our aims were to examine the extent to which TRPA1 and/or TRPV1 ion channels mediate propofol‐induced depressor responses in vivo and to delineate the signaling pathway(s) involved. Methods Mice were subjected to surgery under 1.5‐2.5% sevoflurane gas with supplemental oxygen. After a stable base‐line in MAP was achieved propofol (2.5, 5.0, 10.0 mg/kg/ min) was administered to assess the hemodynamic actions of the intravenous anesthetic. The effect of nitric oxide synthase (NOS) inhibition with L‐NAME and/or calcium‐gated K + channel (BK Ca ) inhibition with Penetrim A (Pen A), alone and in combination, on propofol‐induced decreases in mean arterial pressure (MAP) were assessed in control C57Bl/6J, TRPA1 ‐/‐ , TRPV1 ‐/‐ and TRPAV ‐/‐ mice Results Propofol decreased MAP in control mice and this effect was markedly attenuated in TRPA1 ‐/‐ and TRPAV ‐/‐ mice but unaffected in TRPV1 ‐/‐ mice. Moreover, pretreatment with L‐NAME or Pen A attenuated the decrease in MAP in control and TRPV1 ‐/‐ mice, and combined inhibition abolished the depressor response. In contrast, the markedly attenuated propofol‐induced depressor response observed in TRPA1 ‐/‐ and TRPAV ‐/‐ mice was unaffected by pre‐treatment with Pen A or L‐NAME when used either alone or in combination. Conclusion These data demonstrate for the first time that propofol‐induced depressor responses in vivo are predominantly mediated by TRPA1 ion channels with no involvement of TRPV1 ion channels and includes activation of both NOS and BK Ca .channels.