Prostaglandins do not mediate arteriolar oxygen reactivity

1986 ◽  
Vol 250 (6) ◽  
pp. H1102-H1108 ◽  
Author(s):  
W. F. Jackson
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Intravital Microscopy ◽  
Cheek Pouch ◽  
Cyclooxygenase Inhibitor ◽  
Cremaster Muscle ◽  
Hamster Cheek Pouch ◽  
Nonspecific Effects ◽  
Oxygen Reactivity ◽  
Phospholipase A2 Inhibitors

The hypothesis that prostaglandins mediate arteriolar O2 reactivity was tested by assessing the effects of cyclooxygenase and phospholipase A2 inhibitors on the O2 responses of arterioles in superfused hamster cheek pouch and hamster and rat cremaster muscle preparations by use of intravital microscopy. Superfusion of these three preparations with the cyclooxygenase inhibitor indomethacin (50 microM) completely inhibited the response of the vessels to exogenous arachidonic acid but had no effect on the arteriolar constriction induced by elevation of superfusion solution PO2 from 15 to 150 mmHg. Similar results were obtained in the hamster cheek pouch with another cyclooxygenase inhibitor, meclofenamate, or when indomethacin (5-50 mg/kg) was administered systemically. Dexamethasone (12.7 microM) and quinacrine (10 microM), two reported inhibitors of phospholipase A2, also had no significant effect on arteriolar O2 reactivity in the cheek pouch. At 50 microM, quinacrine significantly depressed arteriolar reactivity to O2, adenosine, methacholine, and phenylephrine, suggesting nonspecific effects. These data do not support the hypothesis that prostaglandins mediate arteriolar O2 reactivity.

Lipoxygenase inhibitors block O2 responses of hamster cheek pouch arterioles

1988 ◽  
Vol 255 (4) ◽  
pp. H711-H716 ◽  
Author(s):  
W. F. Jackson
Keyword(s):  
Oxygen Tension ◽  
Nordihydroguaiaretic Acid ◽  
Cheek Pouch ◽  
Biochemical Pathway ◽  
Adrenergic Agonist ◽  
Hamster Cheek Pouch ◽  
Lipoxygenase Inhibitors ◽  
Cheek Pouches ◽  
Oxygen Reactivity

The hypothesis that a lipoxygenase is involved in arteriolar oxygen reactivity was tested in the superfused hamster cheek pouch preparation by assessment of the effects of three lipoxygenase inhibitors on the response of arterioles to changes in superfusate PO2. Superfusion of hamster cheek pouches with nordihydroguaiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (20 microM ETYA), or 100 microM 1-phenyl-3-pyrazolidone (phenidone) decreased (10 microM NDGA) or eliminated (30 microM NDGA, ETYA, or phenidone) the constriction of arterioles induced by elevation of superfusate oxygen tension. The response of the arterioles to the alpha 1-adrenergic agonist phenylephrine was not significantly affected by these inhibitors, an indication that the decreased oxygen response was not due to a nonspecific decrease in arteriolar reactivity. These data suggest that arteriolar oxygen reactivity in the hamster cheek pouch might involve a lipoxygenase or other noncyclooxygenase oxygen-dependent biochemical pathway that can be inhibited by NDGA, ETYA, and phenidone.

Neutral endopeptidase modulates substance P-induced vasodilation in vivo

1995 ◽  
Vol 78 (2) ◽  
pp. 562-568 ◽  
Author(s):  
X. P. Gao ◽  
I. Rubinstein
Keyword(s):  
Substance P ◽  
Oral Mucosa ◽  
Intravital Microscopy ◽  
Neutral Endopeptidase ◽  
Cheek Pouch ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Arteriolar Diameter ◽  
Significant Concentration

The purpose of this study was to investigate whether neutral endopeptidase (NEP; EC 3.4.24.11) modulates substance P-induced vasodilation in the oral mucosa in vivo. Using intravital microscopy, we measured the diameter of second-order arterioles (44–70 microns) in the hamster cheek pouch during suffusion of capsaicin and substance P. We found that capsaicin (0.1 and 10.0 nM) induced significant concentration-dependent vasodilations (13 +/- 4 and 39 +/- 7% increase from baseline, respectively; P < 0.05) that were significantly potentiated by phosphoramidon (10.0 nM), a selective NEP inhibitor (35 +/- 15 and 61 +/- 12% increase from baseline, respectively; P < 0.05). Substance P (0.1 and 10.0 nM) also induced significant concentration-dependent vasodilations (7 +/- 3 and 25 +/- 8% increase from baseline, respectively; P < 0.05) that were mediated by the COOH-terminal of the molecule. Substance P-induced responses were significantly potentiated by phosphoramidon (34 +/- 9 and 53 +/- 10% increase from baseline, respectively; P < 0.05) and thiorphan (10.0 microM), a selective NEP inhibitor (44 +/- 11 and 53 +/- 10% increase from baseline, respectively; P < 0.05). Substance P-(1–9) had no significant effects on arteriolar diameter. Suffusion of captopril, leupeptin, Bestatin, and DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid together had no significant effects on substance P-induced vasodilation. Phosphoramidon did not potentiate nitroglycerin-induced vasodilation. These data indicate that NEP modulates substance P-induced vasodilation in the hamster cheek pouch in vivo. We suggest that any decrease in tissue NEP activity may amplify neurogenic vasodilation in the oral mucosa.

Arteriolar tone is determined by activity of ATP-sensitive potassium channels

1993 ◽  
Vol 265 (5) ◽  
pp. H1797-H1803 ◽  
Author(s):  
W. F. Jackson
Keyword(s):  
Potassium Channels ◽  
Intravital Microscopy ◽  
Cheek Pouch ◽  
Cremaster Muscle ◽  
Adrenergic Agonists ◽  
Beta Adrenergic Agonists ◽  
Muscle Concentration ◽  
Arteriolar Tone ◽  
Arteriolar Vasodilation

The role of ATP-sensitive potassium channels (KATP) in determining resting arteriolar tone and vasodilator reactivity was assessed in superfused, hamster microcirculatory beds studied via intravital microscopy. Under resting conditions, the selective KATP blocker, glibenclamide, produced concentration-dependent vasoconstriction in both the cheek pouch and the cremaster muscle. Concentration-related constriction of cheek pouch arterioles was also observed with tetrapentylammonium, although this agent appeared to have toxic effects on the microcirculation. Glibenclamide (2 microM) abolished arteriolar vasodilation to cromakalim and pinacidil over a concentration range (10 nM-1 microM) in which these agents are selective KATP agonists and also significantly inhibited adenosine-, carbacyclin-, and isoproterenol-induced vasodilation. In contrast, responses to other vasodilators were not significantly affected [methacholine, forskolin, and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP)] or only slightly depressed (sodium nitroprusside). Thus the activity of KATP determines, in part, resting arteriolar tone in the hamster. Furthermore, vasodilators like adenosine, beta-adrenergic agonists, and prostacyclin appear to act through these ion channels by a mechanism that may not involve cAMP.

Arteriolar oxygen reactivity: where is the sensor?

1987 ◽  
Vol 253 (5) ◽  
pp. H1120-H1126 ◽  
Author(s):  
W. F. Jackson
Keyword(s):  
Oxygen Sensors ◽  
Cheek Pouch ◽  
Global Changes ◽  
Hamster Cheek Pouch ◽  
Oxygen Sensitive ◽  
Oxygen Reactivity ◽  
Arteriolar Diameter

The hypothesis that arterioles are intrinsically sensitive to oxygen was tested by comparing arteriolar diameter responses with local and global PO2 changes in superfused hamster cheek pouch preparations. Local PO2 changes were produced by microapplication of fluid onto the surface of occluded or unoccluded aparenchymal arterioles or by cannulation and perfusion of arterioles in situ. Global changes refer to PO2 changes in the superfusate flowing over the entire preparation. Local, effective PO2 changes had no significant effect on arteriolar diameters. In contrast, global PO2 changes produced significant, reproducible changes in diameter. These observations do not support the hypothesis that arterioles are intrinsically oxygen sensitive, unless the oxygen-sensitive sites are distributed sparsely along the arteriolar tree. The data are consistent with oxygen sensors located either in vessels downstream from 15-micron arterioles (in terminal arterioles, capillaries, or venules) or in the parenchyma. The data also suggest that these sensors detect changes in PO2 and then initiate responses that can be conducted along the vasculature to an arteriole distant from the sensor.

scholarly journals Inhibition of neutrophil migration by a selective inhibitor of matrix metalloproteinase: analysis by intravital microscopy

1995 ◽  
Vol 4 (2) ◽  
pp. 133-137 ◽  
Author(s):  
T. Oda ◽  
M. Katori ◽  
K. Hatanaka ◽  
Y. Nagai
Keyword(s):  
Endothelial Cells ◽  
Basement Membrane ◽  
Matrix Metalloproteinase ◽  
Intravital Microscopy ◽  
Neutrophil Migration ◽  
Selective Inhibitor ◽  
Perivascular Space ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Vascular Lumen

Observation of the microcirculation of the hamster cheek pouch by intravital microscopy revealed five steps of neutrophil migration from the venules after topical application of leukotriene B4to the microvasculature: rolling along the venular wall (Step 1), adhesion to it (Step 2), disappearance from the vascular lumen (Step 3), presence between the endothelial cells and the subendothelial basement membrane (Step 4) and passage through the basement membrane (Step 5). The present study was performed to examine whether a metalloproteinase inhibitor inhibits neutrophil migration at any of the above five steps. Chymostatin and leupeptin did not inhibit any of these five steps. In contrast, FN-439, a selective inhibitor of matrix metalloproteinase, reduced the number of neutrophils in the perivascular space without affecting Steps 1 to 3. It was concluded that neutrophils may use metalloproteinase (collagenase/gelatinase) to penetrate the subendothelial basement membrane.

Venular reactivity in the hamster cheek pouch and cremaster muscle

1986 ◽  
Vol 31 (3) ◽  
pp. 379-383 ◽  
Author(s):  
David N. Damon ◽  
Brian R. Duling
Keyword(s):  
Cheek Pouch ◽  
Cremaster Muscle ◽  
Hamster Cheek Pouch

scholarly journals A novel phospholipase A2 from human placenta

1995 ◽  
Vol 311 (1) ◽  
pp. 147-153 ◽  
Author(s):  
W J Buhl ◽  
L M Eisenlohr ◽  
I Preuss ◽  
U Gehring
Keyword(s):  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Molecular Mass ◽  
Human Placenta ◽  
Type Ii ◽  
Human Term Placenta ◽  
Phospholipases A2 ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipases A2 ◽  
Phospholipase A2 Inhibitors

A major soluble phospholipase A2 of human term placenta was characterized and purified about 15,000-fold to homogeneity. The apparent molecular mass as determined in SDS/polyacrylamide gels is 42 kDa. The enzyme is inhibited by dithiothreitol indicating the presence of disulphide bridges which are essential for activity. Studies with known phospholipase A2 inhibitors revealed no immediate relationship to either secretory or cytosolic phospholipases A2. The placental enzyme prefers liposomes of phosphatidylcholine and has a distinct preference for arachidonic acid in the sn-2 position. It tolerates various detergents. Roughly 10 microM Ca2+ is required for activity, but it cannot be replaced by Mg2+ or Mn2+; Zn2+, Cu2+ and Fe3+ are inhibitory. In immunoblots, the placental enzyme was not detected by two separate antisera specific for type-II phospholipases A2 but reacted very weakly with antisera directed against cytosolic phospholipase A2. From these data we suggest that this enzyme is a novel form of phospholipase A2 which may be involved in arachidonic acid mobilization both during the course of pregnancy and at parturition.

Arteriolar oxygen reactivity is inhibited by leukotriene antagonists

1989 ◽  
Vol 257 (5) ◽  
pp. H1565-H1572 ◽  
Author(s):  
W. F. Jackson
Keyword(s):  
Related Compound ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Leukotriene Antagonists ◽  
Lipoxygenase Inhibitors ◽  
Dose Dependent Fashion ◽  
Leukotriene Receptor ◽  
Oxygen Tensions ◽  
Oxygen Reactivity ◽  
Dose Dependent

Experiments were performed to test the hypothesis that the arteriolar constriction produced by elevated oxygen tensions in the hamster cheek pouch is mediated by a leukotriene. To test this hypothesis, the diameter response of arterioles in superfused hamster cheek pouch preparations to stepwise increases in superfusion solution oxygen content was measured by video microscopy in the absence and 30 min after superfusion with solutions containing inhibitors of the synthesis or actions of leukotrienes. Oxygen-induced constrictions were inhibited in a dose-dependent fashion by two structurally distinct 5-lipoxygenase inhibitors (U 60257 and SC 43251) and two different leukotriene receptor antagonists (SKF 102922 and FPL 55712). Also, all four inhibitors tended to dilate the arterioles under low PO2 conditions. The inhibition of oxygen reactivity appeared to be selective in that arteriolar constrictions induced by topical application of phenylephrine were unaffected (SC 43251, SKF 102922, FPL 55717, and 30 microM U 60257) or only modestly reduced (100 microM U 60257) by the inhibitors. These data are consistent with the hypothesis that a leukotriene, or related compound, mediates arteriolar oxygen reactivity in the hamster cheek pouch.

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