Parenchymal Tissue Cytochrome P450 4A Enzymes Contribute to Oxygen-Induced Alterations in Skeletal Muscle Arteriolar Tone

2002 ◽  
Vol 63 (3) ◽  
pp. 340-343 ◽  
Author(s):  
Jefferson C. Frisbee ◽  
Julian H. Lombard
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome P450 ◽  
Parenchymal Tissue ◽  
Arteriolar Tone ◽  
Cytochrome P450 4A

scholarly journals Skeletal Muscle Interleukin-6 Regulates Hepatic Cytochrome P450 Expression: Effects of 16-Week High-Fat Diet and Exercise

2017 ◽  
Vol 162 (1) ◽  
pp. 309-317 ◽  
Author(s):  
Jakob G Knudsen ◽  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Sabine Gerbal-Chaloin ◽  
Martin Krøyer Rasmussen
Keyword(s):  
Skeletal Muscle ◽  
Cytochrome P450 ◽  
Interleukin 6 ◽  
High Fat Diet ◽  
High Fat ◽  
Diet And Exercise ◽  
P450 Expression ◽  
Hepatic Cytochrome

Biphasic effect of hydrogen peroxide on skeletal muscle arteriolar tone via activation of endothelial and smooth muscle signaling pathways

2004 ◽  
Vol 97 (3) ◽  
pp. 1130-1137 ◽  
Author(s):  
Csongor Csekő ◽  
Zsolt Bagi ◽  
Akos Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Hydrogen Peroxide ◽  
Blood Flow ◽  
Smooth Muscle ◽  
Muscle Blood Flow ◽  
Skeletal Muscle Blood Flow ◽  
Local Regulation ◽  
Prostaglandin H ◽  
Arteriolar Tone

We hypothesized that hydrogen peroxide (H2O2) has a role in the local regulation of skeletal muscle blood flow, thus significantly affecting the myogenic tone of arterioles. In our study, we investigated the effects of exogenous H2O2 on the diameter of isolated, pressurized (at 80 mmHg) rat gracilis skeletal muscle arterioles (diameter of ∼150 μm). Lower concentrations of H2O2 (10−6–3 × 10−5 M) elicited constrictions, whereas higher concentrations of H2O2 (6 × 10−5–3 × 10−4 M), after initial constrictions, caused dilations of arterioles (at 10−4 M H2O2, −19 ± 1% constriction and 66 ± 4% dilation). Endothelium removal reduced both constrictions (to −10 ± 1%) and dilations (to 33 ± 3%) due to H2O2. Constrictions due to H2O2 were completely abolished by indomethacin and the prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist SQ-29548. Dilations due to H2O2 were significantly reduced by inhibition of nitric oxide synthase (to 38 ± 7%) but were unaffected by clotrimazole or sulfaphenazole (inhibitors of cytochrome P-450 enzymes), indomethacin, or SQ-29548. In endothelium-denuded arterioles, clotrimazole had no effect, whereas H2O2-induced dilations were significantly reduced by charybdotoxin plus apamin, inhibitors of Ca2+-activated K+ channels (to 24 ± 3%), the selective blocker of ATP-sensitive K+ channels glybenclamide (to 14 ± 2%), and the nonselective K+-channel inhibitor tetrabutylammonium (to −1 ± 1%). Thus exogenous administration of H2O2 elicits 1) release of PGH2/TxA2 from both endothelium and smooth muscle, 2) release of nitric oxide from the endothelium, and 3) activation of K+ channels, such as Ca2+-activated and ATP-sensitive K+ channels in the smooth muscle resulting in biphasic changes of arteriolar diameter. Because H2O2 at low micromolar concentrations activates several intrinsic mechanisms, we suggest that H2O2 contributes to the local regulation of skeletal muscle blood flow in various physiological and pathophysiological conditions.

Microvascular response to blockade of prostaglandin synthesis in rat skeletal muscle

1982 ◽  
Vol 243 (1) ◽  
pp. H51-H60 ◽  
Author(s):  
J. E. Faber ◽  
P. D. Harris ◽  
I. G. Joshua
Keyword(s):  
Skeletal Muscle ◽  
Cremaster Muscle ◽  
Local Blood Flow ◽  
Local Inhibition ◽  
Microvascular Response ◽  
Before And After ◽  
Endogenous Prostaglandins ◽  
The Moment ◽  
Arteriolar Tone ◽  
Arteriolar Diameter

The contribution of endogenous prostaglandins (PGs) to the control of arteriolar diameter in the microcirculation is incompletely defied and has only been studied in drug-anesthetized animals. To test the possibility that endogenous PGs are tonically released to exert a net dilator influence at certain levels in the microcirculation, television microscopy was used to quantitate the arteriolar responses in the rat cremaster muscle to local blockade of PG synthesis with indomethacin. Rats were decerebrated by a midcollicular transection and were allowed to recover from surgical anesthesia. The cremaster muscle with intact circulation and innervation was suspended by sutures in a temperature-controlled Krebs bath. Diameters, vasomotion frequency, and vasomotion amplitude of arterioles at several anatomic levels were measured before and after local inhibition of PG synthesis in the presence and absence of alpha-adrenergic receptor blockade. Inhibition of PG synthesis produced marked constriction (42-66% of control) at all arteriolar levels, with greater responses occurring in the smaller arterioles. PG synthesis blockade increased vasomotion frequency in arterioles that exhibited spontaneous vasomotion during control periods, and blockade induced vasomotion in vessels lacking spontaneous vasomotion. Pretreatment with phentolamine significantly attenuated the constriction and augmentation of vasomotion. These data indicate that dilator PGs participate in the moment-to-moment regulation of arteriolar tone and local blood flow in skeletal muscle. Further, their mechanism of action may involve alterations in neuronal norepinephrine release or alpha-receptor sensitivity.

REGULATION AND INHIBITION OF ARACHIDONIC ACID ω-HYDROXYLASES AND 20-HETE FORMATION

2005 ◽  
Vol 45 (1) ◽  
pp. 413-438 ◽  
Author(s):  
Deanna L. Kroetz ◽  
Fengyun Xu
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Enzyme Inhibitors ◽  
Biological Effects ◽  
Biological Significance ◽  
Substrate Selectivity ◽  
Altered Expression ◽  
Important Pathway ◽  
And Function ◽  
Cytochrome P450 4A

Cytochrome P450–catalyzed metabolism of arachidonic acid is an important pathway for the formation of paracrine and autocrine mediators of numerous biological effects. The ω-hydroxylation of arachidonic acid generates significant levels of 20-hydroxyeicosatetraenoic acid (20-HETE) in numerous tissues, particularly the vasculature and kidney tubules. Members of the cytochrome P450 4A and 4F families are the major ω-hydroxylases, and the substrate selectivity and regulation of these enzymes has been the subject of numerous studies. Altered expression and function of arachidonic acid ω-hydroxylases in models of hypertension, diabetes, inflammation, and pregnancy suggest that 20-HETE may be involved in the pathogenesis of these diseases. Our understanding of the biological significance of 20-HETE has been greatly aided by the development and characterization of selective and potent inhibitors of the arachidonic acid ω-hydroxylases. This review discusses the substrate selectivity and expression of arachidonic acid ω-hydroxylases, regulation of these enzymes during disease, and the application of enzyme inhibitors to study 20-HETE function.

Impaired hemorrhage tolerance in the obese Zucker rat model of metabolic syndrome

2006 ◽  
Vol 100 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Jefferson C. Frisbee
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Arterial Pressure ◽  
Blood Volume ◽  
Zucker Rats ◽  
Total Blood Volume ◽  
Total Blood ◽  
Muscle Perfusion ◽  
The Metabolic Syndrome ◽  
Arteriolar Tone

As obese Zucker rats (OZR) manifesting the metabolic syndrome exhibit enhanced vascular adrenergic constriction and potentially an enhanced adrenergic activity vs. lean Zucker rats (LZR), this study tested the hypothesis that OZR exhibit an improved tolerance to progressive hemorrhage. Preliminary experiments indicated that, corrected for body mass, total blood volume was reduced in OZR vs. LZR. Anesthetized LZR and OZR had a cremaster muscle prepared for in situ videomicroscopy and had renal, splanchnic, hindlimb, and skeletal muscle perfusion monitored with flow probes. Arterial pressure, arteriolar reactivity to norepinephrine, and tissue/organ perfusion were monitored after either infusion of phentolamine or successive withdrawals of 10% total blood volume. Phentolamine infusion indicated that regional adrenergic tone under control conditions differs substantially between LZR and OZR, whereas with hemorrhage OZR exhibit decompensation in arterial pressure before LZR. Renal, distal hindlimb, and skeletal muscle perfusion decreased more rapidly and to a greater extent in OZR vs. LZR after hemorrhage. In contrast, hemorrhage-induced reductions in splanchnic perfusion in OZR lagged behind those in LZR, although a similar maximum reduction was ultimately attained. With increasing hemorrhage, cremasteric arteriolar tone increased more in OZR than LZR, and this increase in active tone was entirely due to an elevated adrenergic contribution. Norepinephrine-induced arteriolar constriction was greater in OZR vs. LZR under control conditions and during hemorrhage, with arterioles from OZR demonstrating early closure vs. LZR. These results suggest that a combination of reduced blood volume and elevated peripheral adrenergic constriction contribute to impaired hemorrhage tolerance in OZR.

scholarly journals Tissue Sources of Cytochrome P450 4A and 20-HETE Synthesis in Rabbit Lungs

1998 ◽  
Vol 19 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Daling Zhu ◽  
Richard M. Effros ◽  
David R. Harder ◽  
Richard J. Roman ◽  
Elizabeth R. Jacobs
Keyword(s):  
Cytochrome P450 ◽  
Cytochrome P450 4A

Expression of cytochrome P450 4A mRNA in mouse lung: effect of clofibrate and interleukin-1beta

2004 ◽  
Vol 18 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Renaud Le Bouquin ◽  
Alain Lugnier ◽  
Nelly Frossard ◽  
Francoise Pons
Keyword(s):  
Cytochrome P450 ◽  
Mouse Lung ◽  
Interleukin 1Beta ◽  
Cytochrome P450 4A
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