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W F Jackson

Publications and source records attributed to W F Jackson.

At least 37 records · Page 2Linked to original sources
PubMed1991

Rhythmic smooth muscle activity in hamster aortas is mediated by continuous release of NO from the endothelium.

Hamster aortas display endothelium-dependent, agonist-induced rhythmic contractions. However, the mechanism responsible for these oscillations is not known. Therefore, we investigated the possible role of nitric oxide (NO) on phenylephrine-induced rhythmicity in rings and segments of thoracic aortas of the hamster. We found that hamster aortas release NO, as detected by activation of purified soluble guanylate cyclase. The release of NO was abolished by mechanical removal of the endothelium or by exposure of the vessels to NG-nitro-L-arginine (NAG), a stereospecific selective inhibitor of NO synthesis. Correlated with the tonic release of NO was an elevation in guanosine 3',5'-cyclic monophosphate (cGMP) content in the vessels that could also be abolished by removal of the endothelium or treatment with NAG. The same procedures inhibited phenylephrine-induced isometric tension or diameter oscillations. Rhythmicity could be restored by exposure to the nitrovasodilator sodium nitroprusside, which increased cGMP levels in the aortas, or by exposure to the permeant analogue of cGMP, 8-BrcGMP. The beta-adrenergic agonist isoproterenol, as well as the cAMP analogue dibutyryl cAMP, failed to produce rhythmic contractions in either preparation. These data indicate that endothelium-derived NO, which stimulates the production of cGMP in the vascular smooth muscle, is the signal that leads to the observed rhythmic oscillations in smooth muscle mechanical activity.

Animals↗
PubMed1991

Modulation of vascular reactivity to serotonin in the dog lung.

Experiments were conducted to compare the effects of cyclooxygenase inhibition (COI) on vascular reactivity to serotonin (5-HT) in the isolated blood-perfused canine left lower lung lobe (LLL) and in isolated canine intrapulmonary lobar artery rings with and without a functional endothelium. LLLs (n = 6), perfused at constant blood flow, were challenged with bolus doses of 50, 100, and 250 micrograms 5-HT before COI, after COI with 45 microM meclofenamate, and after infusion of prostacyclin (PGI2) during COI. Lobar vascular resistance was segmentally partitioned by venous occlusion. Pulmonary arterial pressure increased from 13.5 +/- 1.0 to 16.3 +/- 0.8 cmH2O (P less than 0.01) after COI but declined to 13.1 +/- 1.1 cmH2O (P less than 0.01) subsequent to PGI2 infusion (91.3 +/- 14.5 ng.min-1.g LLL-1). The pulmonary arterial pressure changes were related to changes in postcapillary resistance. The dose-dependent pressor response to 5-HT was potentiated by COI (P less than 0.01) but reversibly attenuated (P less than 0.05) by PGI2 infusion. Isolated intrapulmonary artery rings (2-4 mm diam) exhibited a dose-related increase in contractile tension to 5-HT. The response to 5-HT was enhanced (P less than 0.05) in rings devoid of a functional endothelium. However, COI (10 microM indomethacin) did not alter (P greater than 0.05) the dose-related increase in contractile tension to 5-HT in rings with an intact endothelium. Our results suggest that both PGI2 and endothelium-derived relaxing factors modulate pulmonary vascular reactivity to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nitric oxide does not mediate arteriolar oxygen reactivity.

Endothelium-derived relaxing factor, which is believed to be nitric oxide (NO), mediates vasodilation of arteries perfused with hypoxic solutions. The purpose of the present study was to determine if NO mediates the response of arterioles in the hamster cheek pouch to changes in superfusion solution PO2. This was accomplished by comparison of constriction of fourth order arterioles to increases in superfusate PO2 before and during superfusion with NG-nitro-L-arginine (L-NAG), a stereospecific inhibitor of NO synthesis. The efficacy of L-NAG was assessed by comparison of dilations induced by topical application of methacholine (MCH), an endothelium-dependent vasodilator. We found that 10-15 min superfusion with 30 microM L-NAG significantly inhibited MCH-induced arteriolar dilation. However, this concentration of L-NAG had no significant effect on resting arteriolar diameters, O2-induced constrictions, constrictions induced by phenylephrine or dilations induced by sodium nitroprusside (SNP). Increasing the concentration of L-NAG to 100 microM similarly inhibited MCH-induced dilations, but did not affect SNP reactivity and may have increased vasoconstriction induced by O2. Thus, effective inhibition of NO synthesis in the hamster cheek pouch does not inhibit responses to elevated oxygen. Therefore NO does not mediate arteriolar O2 reactivity in this tissue. Furthermore, there is little evidence for tonic modulation of arteriolar reactivity by NO in the microvessels observed in this study.

Animals↗
PubMed1989

The endothelium-derived relaxing factor.

Over the past 25 years, it has become clear that the vascular endothelium plays an important role in the function of the cardiovascular system. Most recently, it has been established that endothelial cells can determine or modulate the response of vascular smooth muscle cells to vasoactive stimuli, by production of a labile factor (or factors) that has been named the "Endothelium-Derived Relaxing Factor" (EDRF). While much remains to be learned about the pathways responsible for the production and the effects of EDRF, and its role in cardiovascular physiology, it is apparent that the loss of this endothelium-derived vasodilator can have profound effects on vascular pharmacology and physiology that could be important to the pathologies associated with disease states.

Animals↗
PubMed1989

Arteriolar oxygen reactivity is inhibited by leukotriene antagonists.

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.

Animals↗
PubMed1988

Lipoxygenase inhibitors block O2 responses of hamster cheek pouch arterioles.

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.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1988

Oscillations in active tension in hamster aortas: role of the endothelium.

Hamster thoracic aortas displayed rhythmic oscillations in active tension when stimulated with the alpha 1-adrenergic agonist, phenylephrine, prostaglandin F2 alpha (PGF2 alpha), and a number of other agonists, but not when activated with K+. These oscillations were not affected by adrenergic or cholinergic antagonists, or an inhibitor of prostaglandin synthesis. However, removal of the endothelium from these vessels eliminated this rhythmic activity. Furthermore, exposure to methylene blue or hemoglobin (known inhibitors of endothelium-dependent phenomena) significantly reduced the amplitude and the frequency of the oscillations. Removal of extracellular calcium ions or treatment with the calcium channel blocker, verapamil, also inhibited the oscillations even when active tension was maintained. These data suggest that the oscillations in agonist-induced active tension depend on a functional endothelium, and possibly an endothelium-derived factor, and the influx of extracellular calcium. This study also demonstrates that, like most other species, hamster aortas display endothelium-dependent relaxation to muscarinic agonists, such as methacholine, and the calcium ionophore A23187.

Animals↗
PubMed1987

Arteriolar oxygen reactivity: where is the sensor?

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.

Animals↗
PubMed1986

Prostaglandins do not mediate arteriolar oxygen reactivity.

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.

Animals↗
PubMed1983

Toxic effects of silver-silver chloride electrodes on vascular smooth muscle.

We found that silver, either as silver metal or silver chloride, exerted toxic effects on the smooth muscle of isolated cannulated hamster cheek pouch arterioles. Silver initially stimulated the smooth muscle, producing a marked vasoconstriction. The vessels then dilated back to control diameters. Once the arterioles began to dilate, they became refractory to norepinephrine or potassium stimulation. We caution the use of silver in the presence of smooth muscle, especially when tissue mass is small or free protein concentration is low.

Animals↗
PubMed1983

The oxygen sensitivity of hamster cheek pouch arterioles. In vitro and in situ studies.

We tested the hypothesis that a parenchymally derived mediator is required for arterioles to exhibit oxygen sensitivity. To that end, the parenchyma was dissected and removed from around hamster cheek pouch arterioles, and the oxygen sensitivity of these "aparenchymal arteriolar segments" was studied, either in vitro, after cannulation, or in situ. Arteriolar segments in situ with and without parenchyma had similar oxygen sensitivities (20% constriction as Po2 increased from 15 to 150 mm Hg). Arteriolar occlusion, which eliminated blood flow in the in situ aparenchymal segments, did not eliminate their oxygen sensitivity. The oxygen-induced constriction in the occluded aparenchymal segments was blunted but not eliminated by covering the segments with glass plates to prevent changes in Po2 from occurring around these vessels. We hypothesized that propagation of a portion of the oxygen response might explain the persistent response in the covered and occluded arteriolar segments. Oxygen sensitivity could be shown in only 32% of the in vitro cannulated arterioles (16% mean constriction as Po2 increased from 20 to 150 mm Hg). In contrast, 75% of aparenchymal arterioles were sensitive to changes in Po2 in situ. These data led us to reject the hypothesis that a parenchymally derived mediator is absolutely required for arterioles to exhibit oxygen sensitivity. We infer that the oxygen sensitivity of hamster cheek pouch arterioles results partially or totally from the local action of oxygen on some component of the arteriolar wall or blood, that a portion of the oxygen response may be the result of a propagated phenomenon, and that the oxygen-sensitive component is fragile and is easily lost in preparation for in vitro measurements or in cannulation. It is emphasized that the O2 sensor need not reside in vascular smooth muscle.

Animals↗
PubMed1982

A comparison of microvascular estimates of capillary blood flow with direct measurements of total striated muscle flow.

Relations between bulk flow into skeletal muscles and microscopically observed capillary flow are compared and disagreements between the two types of data are found. Mean capillary blood velocity was computed using data from a variety of literature sources and assuming uniform distribution of flow through a parallel array of capillaries. The average ratio of measured red cell velocity to computed mean blood velocity was 4.4 +/- 1.0. This is statistically different from the measured value reported in the literature of 1.3. In the cremaster muscle, bulk flow of red cells into the tissue was not statistically different from the measured flux of single red cells through capillaries observed microscopically. The factors which contribute to this apparent agreement of mass balance are not understood, however. Capillary hematocrit is very low and the low capillary hematocrit has been explained by others by the presence of nonuniform flow distribution among the capillaries (shunts or flow heterogeneity). However, for the cremaster data sample, red cells were accounted for in observed capillary flow and red cells were distributed rather homogeneously through the capillaries. This suggests that low capillary hematocrit is the result neither of shunting of red cells around the capillaries nor of nonuniform capillary red cell flow alone. There does not appear to be any well-accepted phenomenon which will explain the findings of: 1) low apparent mean blood velocity; 2) low and variable hematocrit; and 3) apparent conservation of red cell mass. The findings can be reconciled, however, if the capillary rheology is more complex than heretofore anticipated, with a stabilized layer of plasma on the inner surface of the capillary in the order of a 1-micrometer thickness. While there is little direct evidence for such a layer at this time, data which are consistent with the possible existence of such a layer are presented.

Animals↗
PubMed1981

Factors affecting 3H2O transfer capacity of isolated perfused trout gills.

Tritiated water (3H2O) transfer capacity (PdA) and vascular impedance (Zg) of isolated trout (Salmo gairdneri) gills perfused with or without epinephrine were studied under conditions of altered osmotic gradients, fluid stirring, perfusion rate (Qa), and efferent pressure (Pe). Transfer capacity was unaffected by osmotic gradients, indicating that 3H2O moves across gills by diffusion and that PdA is independent of hydraulic water movement. Fluid stirring increased PdA asymptotically, suggesting that boundary layers significantly affect diffusion across isolated gills. Transfer capacity was directly related to Qa; Zg was inversely related to Qa. The PdA results can be explained in terms of lamellar recruitment and the distribution of flow between secondary lamellae. Increased Qa reduced Zg due to recruitment and distension of gill vessels. Elevated Pe decreased Zg and PdA. The effects of Pe on Zg resulted from distension of the gill vasculature and increased venous drainage, whereas the effects of Pe on PdA can be explained by changes in the distribution of perfusion between secondary lamellae.

Animals↗
PubMed1977

A new textbook.

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