Warm molecular gas temperature distribution in six local infrared bright Seyfert galaxies

<p><b>A, C, E and G</b>: Summarized data depicting the effect of L-NAME (100 μM) or endothelium removal (denuded) on propofol-induced (does-dependent) changes in luminal diameter in coronary microvessels obtained from control, TRPV1^-/-, TRPA1^-/- and TRPAV^-/- mice, respectively (<i>n</i> = 12). <b>B, D, F and H</b>: Summarized data depicting the effect of Pen A (50 μM) alone and in combination with L-NAME on propofol-induced changes in luminal diameter in coronary microvessels obtained from control, TRPV1^-/-, TRPA1^-/- and TRPAV^-/- mice, respectively (<i>n</i> = 12). Data are expressed as % relaxation ± SEM. *<i>P</i>< 0.05 vs. control.</p

Propofol causes vasodilation in vivo via TRPA1 ion channels: role of nitric oxide and BKCa channels.

Transient receptor potential (TRP) ion channels of the A1 (TRPA1) and V1 (TRPV1) subtypes are key regulators of vasomotor tone. Propofol is an intravenous anesthetic known to cause vasorelaxation. Our objectives 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.Mice were subjected to surgery under 1.5-2.5% sevoflurane gas with supplemental oxygen. After a stable baseline in mean arterial pressure (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 (BKCa) inhibition with Penetrim A (Pen A), alone and in combination, on propofol-induced decreases in mean arterial pressure were assessed in control C57Bl/6J, TRPA1-/-, TRPV1-/- and double-knockout mice (TRPAV-/-).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.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 BKCa channels

Propofol induced changes in MAP in TRPA1^-/- and TRPAV^-/- mice: Panels A and B: Summarized data depicting the effect of L-NAME (100 mg/kg/min) on propofol-induced changes in MAP in TRPA1^-/- and TRPAV^-/- mice.

<p>Panels <b>C</b> and <b>D:</b> Summarized data depicting the effect of Pen A (50ug/kg/min) on propofol-induced changes in MAP in TRPA1^-/- and TRPAV^-/- mice. Panels <b>E</b> and <b>F:</b> Summarized data depicting the effect of L-NAME and Pen A in combination on propofol-induced changes in MAP in control and TRPA1^-/- and TRPAV^-/- mice. Data are means ± SEM. *<i>P</i><0.05 compared to baseline. <i>n</i> = 6 mice in each group.</p

Propofol induced changes in MAP in Control and TRPV1^-/- mice: Panels A and B: Summarized data depicting the effect of L-NAME (100 mg/kg/min) on propofol-induced changes in MAP in control and TRPV1^-/- mice.

<p>Panels <b>C</b> and <b>D:</b> Summarized data depicting the effect of Pen A (50 ug/kg/min) on propofol-induced changes in MAP in control and TRPV1^-/- mice. Panels <b>E</b> and <b>F:</b> Summarized data depicting the effect of L-NAME and Pen A in combination on propofol-induced changes in MAP in control and TRPV1^-/- mice. Data are means ± SEM. *<i>P</i><0.05 compared to baseline. #<i>P</i><0.05 compared to control. <i>n</i> = 6 mice in each group.</p

Baseline Hemodynamics.

<p>Values are represented as Mean ± SE and were obtained after addition of hexamethonium. Body weights were recorded before anesthesia [Control: n = 26; TRPA1 ^-/-: n = 12; TRPV1^-/-: n = 12 and TRPAV^-/-: n = 12]. MAP = Mean Arterial Pressure.</p><p>(*) denotes significance from control p<0.05.</p><p>Baseline Hemodynamics.</p

A schematic representation showing the proposed mechanisms by which propofol causes vasodepressor responses <i>in-vivo</i>.

<p>A schematic representation showing the proposed mechanisms by which propofol causes vasodepressor responses <i>in-vivo</i>.</p

TRPA1 and TRPV1 contribute to propofol-mediated antagonism of U46619-induced constriction in murine coronary arteries.

Transient receptor potential (TRP) ion channels have emerged as key components contributing to vasoreactivity. Propofol, an anesthetic is associated with adverse side effects including hypotension and acute pain upon infusion. Our objective was to determine the extent to which TRPA1 and/or TRPV1 ion channels are involved in mediating propofol-induced vasorelaxation of mouse coronary arterioles in vitro and elucidate the potential cellular signal transduction pathway by which this occurs.Hearts were excised from anesthetized mice and coronary arterioles were dissected from control C57Bl/6J, TRPA1-/-, TRPV1-/- and double-knockout mice (TRPAV-/-). Isolated microvessels were cannulated and secured in a temperature-controlled chamber and allowed to equilibrate for 1 hr. Vasoreactivity studies were performed in microvessels pre-constricted with U46619 to assess the dose-dependent relaxation effects of propofol on coronary microvascular tone.Propofol-induced relaxation was unaffected in vessels obtained from TRPV1-/- mice, markedly attenuated in pre-constricted vessels obtained from TRPA1-/- mice and abolished in vessels obtained from TRPAV-/- mice. Furthermore, NOS inhibition with L-NAME or endothelium denuding abolished the proporfol-induced depressor response in pre-constricted vessels obtained from all mice. In the absence of L-NAME, BKCa inhibition with penitrem A markedly attenuated propofol-mediated relaxation in vessels obtained from wild-type mice and to a lesser extent in vessels obtained from TRPV1-/-, mice with no effect in vessels obtained from TRPA1-/- or TRPAV-/- mice.TRPA1 and TRPV1 appear to contribute to the propofol-mediated antagonism of U46619-induced constriction in murine coronary microvessels that involves activation of NOS and BKCa