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S Rounds

Publications and source records attributed to S Rounds.

At least 37 records · Page 2Linked to original sources
PubMed1997

Group education sessions and compliance with nasal CPAP therapy.

STUDY OBJECTIVES: To determine an effective means of improving compliance with nasal continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). DESIGN: Retrospective chart review. SETTING: An outpatient clinic at a Veterans Affairs Medical Center. PATIENTS: Seventy-three patients with OSA. INTERVENTIONS: Hour meters on CPAP machines provided documentation of nightly machine use. A 2-h group CPAP clinic, scheduled every 6 months, provided education, support, symptom treatment, and equipment monitoring for all CPAP patients. RESULTS: Twenty-five patients had hour meter readings taken at their first CPAP clinic. In these patients, nightly CPAP use increased from 5.2 +/- 0.6 to 6.3 +/- 0.6 h per night after attendance at one CPAP clinic (p < 0.05). CPAP use increased from 5.2 +/- 0.5 before CPAP clinic to 6.3 +/- 0.6 h per night after attendance at all subsequent CPAP clinics for 34 patients (p < 0.05), an improvement that was sustained over 605 +/- 34 days. Twenty-nine percent of patients increased nightly CPAP use by at least 2 h, while only 6% decreased by > or = 2 h (p < 0.025). Patients receiving supplemental oxygen had higher CPAP use prior to CPAP clinic compared to patients not receiving oxygen (p < 0.05). CONCLUSIONS: Attendance in a group clinic designed to encourage patient compliance with CPAP therapy provided a simple and effective means of improving treatment of OSA.

Adult↗
PubMed1996

Mechanism of ATP-induced leukocyte adherence to cultured pulmonary artery endothelial cells.

Previously we have shown that ATP enhances the adherence of HL-60 cells and human neutrophils to bovine pulmonary artery endothelial cells. The current investigations extend earlier findings by showing that ATP and UTP dose-dependently stimulate human neutrophil adherence to human pulmonary artery endothelial cells. We have also explore the mechanisms of ATP- and UTP-stimulated adherence. We have found that fucose, a component of selectin receptors, inhibits ATP-stimulated HL-60 cell-bovine pulmonary artery endothelial cell adhesion. Additionally, pretreatment of HL-60 cells with neuraminidase abolishes ATP enhancement. However, fucose does not affect ATP- or thrombin-induced adhesion of freshly isolated human neutrophils to human endothelial cells. Antibodies to human P-selection intercellular adhesion molecule (ICAM)-1, and the beta-subunit of CD11/CD18 do not alter ATP-induced adherence of HL-60 cells to bovine endothelial cells. Similarly, antibodies to human P-selectin and ICAM-1 do not inhibit human neutrophil-human pulmonary artery endothelial cell adhesion. The platelet-activating factor receptor antagonists, WEB-2086 and L-659,989, are effective in attenuating ATP- and UTP-stimulated adherence. Preincubation of neutrophils or human pulmonary artery endothelial cells with ATP or UTP also enhances adherence, an effect that is blocked by L-659,989. Thus platelet activating factor, associated with both neutrophils and endothelial cells, mediates ATP- and UTP-induced neutrophil adherence. ATP, released during vascular injury, may exacerbate neutrophil-endothelial cell interaction and thereby contribute to neutrophil-induced injury.

Adenosine Triphosphate↗
PubMed1996

Effect of ATP-induced permeabilization on loading of the Na+ probe SBFI into endothelial cells.

The fluoroprobe sodiumbinding benzofuran isophthalate (SBFI) is used to measure intracellular cytosolic sodium concentration ([Na]i). A problem with the use of this probe is the difficulty in loading it into cells. ATP reversibly increases membrane permeability of some cells via activation of receptors of the tetrabasic form of ATP (ATP4-). We investigated the effect of ATP-induced membrane permeabilization on loading of the acetoxymethyl ester (AM) form of SBFI (SBFI-AM) into bovine pulmonary arterial endothelial cells. Monolayers were incubated in a series of solutions that reversibly opened pores, loaded the fluoroprobe, and finally sealed the proes. ATP (1-5 mM) or 3'-O-(4-benzoyl)benzoyl-ATP (0.1-1 mM), an analogue 30-100x more specific for ATP4- receptors, was utilized to permeabilize the cell membrane. The signal-to-background ratio of the intracellular SBFI fluorescent signal was used as an indicator of the effectiveness of dye loading. ATP and 3'-O-(4-benzoyl)benzoyl-ATP significantly increased the signal-to-background ratio compared with the values obtained with the standard dye-loading procedure without ATP, indicating that permeabilization increased SBFI-AM entry into the cells. The permeabilization procedure produced a small decrease in cell viability, as determined with a fluorescent viability assay (ethidium dimer uptake), compared with the standard method of loading SBFI-AM. We used the procedure to measure baseline [Na]i and changes in [Na]i after the administration of ouabain (10(-4) M) and monensin (10(-5) M). Baseline [Na]i with this procedure (19.7 +/- 2.7 mM; n = 15 monolayers) was similar to measurements made in other cell types with the standard method of loading the probe. We conclude that 1) the ATP-induced permeabilization technique is an improved dye-loading method for SBFI-AM in endothelial cell monolayers that facilitates measurement of [Na]i and 2) these data suggest the presence of an ATP4 pore-forming mechanism in this cell type.

Adenosine Triphosphate↗
PubMed1995

Extracellular nucleotides stimulate leukocyte adherence to cultured pulmonary artery endothelial cells.

Adenosine, ATP, and various nucleotides were examined for their effects on the adherence of leukocytes to bovine pulmonary artery endothelial cells. Extracellular ATP enhanced adherence of HL-60 cells and human neutrophils to endothelial cells in a dose-dependent fashion. Maximal adherence occurred after 15 min coincubation of ATP and HL-60 cells or neutrophils with endothelial cells. ATP stimulation was mediated by direct effects on both HL-60 cells and endothelial cells. The potency profile of various nucleotides was ATP = 2-MeSATP > beta,gamma-CH2ATP, indicative of a P2y receptor. Interestingly, UTP was as potent as ATP in stimulating HL-60 cell adherence, suggesting the presence of a pyrimidine nucleotide receptor. Photoaffinity labeling of endothelial cells with 8-Az-[alpha-32P]ATP showed the presence of two ATP binding proteins of 48 and 87 kDa. ATP and 2-MeSATP inhibited binding by both proteins. Labeling of the 87-kDa protein was inhibited by beta,gamma-CH2ATP, whereas UTP blocked binding by the 48-kDa protein. Thus photoaffinity labeling experiments support the proposal that endothelial cells possess two ATP receptors, one of which is a P2u nucleotide receptor. These findings show that extracellular nucleotides enhance leukocyte adherence to endothelial cells. Nucleotide release into the extracellular space may be one mechanism of exacerbating vascular cell injury relevant to conditions such as adult respiratory distress syndrome and septic shock.

Adenosine Triphosphate↗
PubMed1994

Platelet-activating factor (PAF)-induced platelet aggregation. Modulation by plasma adenosine and methylxanthines.

This study examined the role of plasma adenosine in the modulation of platelet-activating factor (PAF) activity on platelet aggregation and serotonin (5-HT) release in human platelet-rich plasma (PRP). In addition, the effects of methylxanthines (e.g. theophylline and caffeine) were studied on PAF-induced platelet aggregation in PRP isolated from blood samples from healthy subjects. Also, PAF-induced platelet aggregation was examined in PRP samples of patients receiving theophylline treatment. These studies demonstrate that plasma adenosine levels (0.1 to 0.3 microM) play a key role in negative modulation of PAF activity on platelet aggregation and 5-HT release. After depletion of plasma adenosine, the platelet-aggregating activity of PAF was increased greatly (> 10-fold). PAF at concentrations of 0.1 to 12 microM caused no 5-HT release in PRP containing normal amounts of adenosine (blood collected in the presence of 2'-deoxycoformycin and dilazep), whereas PAF at 0.1 microM caused 5-HT release (45%) in adenosine-depleted PRP, demonstrating that plasma adenosine is much more inhibitory of 5-HT release than platelet aggregation. The adenosine antagonists theophylline (50 microM), caffeine (50 microM) and a xanthine derivative, 3,7-dimethyl-l-propargylxanthine (DMPX, 10 microM) (a more specific adenosine A2 receptor antagonist), potentiated PAF activity on platelet aggregation in PRP samples containing adenosine. Also, patients receiving theophylline treatments showed significantly greater platelet aggregation induced by PAF in their PRP samples. PAF induced a rapid increase (80% in 15 sec) in intracellular Ca2+ mobilization, which was strongly inhibited by adenosine (IC50, 0.3 microM). Our studies suggest that agents that can increase plasma adenosine levels (e.g. inhibitors of adenosine uptake and adenosine metabolism) or methylxanthines may be useful in altering (inhibiting or enhancing, respectively) PAF actions on platelets and other tissues.

Adenosine↗
PubMed1994

Effects of endotoxin injury on endothelial cell adenosine metabolism.

Adenosine is a potent autocoid that acts as a vasodilator and modulator of inflammatory responses. Endothelial cells possess several mechanisms for altering circulating levels of adenosine and are capable of release of adenosine metabolites. We used cultured bovine aortic and main pulmonary arterial endothelial cells to determine whether endotoxin can alter adenosine uptake or release of adenosine metabolites. We found that 24 hours, but not 6 hours, of incubation with endotoxin caused endothelial cell injury, as assessed by cell detachment and chromium 51 release. Despite this injury the extent of [3H]adenosine uptake was unchanged. Using thin-layer chromatography to identify adenosine and its metabolites, we found that [3H]adenosine was primarily metabolized into intracellular hypoxanthine and adenine nucleotides. After 1, 6, and 24 hours of incubation with endotoxin there was an increase in extracellular adenosine metabolites, which was accompanied by decreases in the level of intracellular adenosine 5'-triphosphate. The appearance of adenosine metabolites in culture supernatants was a more sensitive measure of endothelial cell injury than 51Cr release or adherent cell number. The extracellular purine metabolite observed in response to endotoxin injury was mainly hypoxanthine. Our findings suggest that hypoxanthine release is an early event in endotoxin-induced endothelial cell injury. Because hypoxanthine may act as a substrate for xanthine oxidase, resulting in toxic oxidant production, its release has the potential of exacerbating vascular injury caused by endotoxin.

Adenine Nucleotides↗
PubMed1993

A simple assay for ecto-5'-nucleotidase using intact pulmonary artery endothelial cells. Effect of endotoxin-induced cell injury.

Adenosine may be protective in acute vascular injury by inhibiting platelet aggregation and neutrophil oxidant release. In contrast, adenine nucleotides, which may be released with acute vascular injury, stimulate platelet aggregation and neutrophil oxidant release. Ectonucleotidases, membrane enzymes that catabolize extracellular nucleotides, are the primary mechanism for degrading circulating nucleotides to adenosine. Ecto-5'-nucleotidase converts extracellular AMP to adenosine. We hypothesized that endothelial cell injury alters ecto-5'-nucleotidase activity. Using a novel assay first reported by Jamal et al. (Biochem J 250: 369-373, 1988) with rat adipocytes, we studied the properties of ecto-5'-nucleotidase in intact monolayers of cultured bovine pulmonary artery endothelial cells (BPAEC) and examined the effect of endotoxin on enzyme activity. The assay uses a fluorescent analog of AMP, 1,N6-etheno-AMP (E-AMP), as the substrate for ecto-5'-nucleotidase, and measures ethenoadenosine (E-Ado) formation. Etheno-AMP in Hepes buffer, pH 7.4, at 22 degrees, was added to confluent monolayers of BPAEC; samples of supernatant were collected after various intervals, and E-AMP and E-Ado were quantitated by HPLC. Using these methods we found a Km of 15 +/- 6 microM, a pH optimum of 7.48, minimal effect of MgCl2 or CaCl2 at physiologic pH, and inhibition by alpha,beta-methylene ADP, a known 5'-nucleotidase inhibitor. We established that the monolayer assay was indeed measuring cell surface associated 5'-nucleotidase. To determine the effect of endotoxin, we incubated confluent monolayers with endotoxin in Minimal Essential Medium plus 10% fetal bovine serum for 24 hr, washed them, and assessed the conversion of E-AMP to E-Ado by the endotoxin-injured cells. Endotoxin stimulated endothelial ecto-5'-nucleotidase activity. This increase in 5'-nucleotidase activity in response to endotoxin injury may represent an important clearance mechanism for circulating adenine nucleotides and may be protective in acute vascular injury by increasing adenosine production.

5'-Nucleotidase↗
PubMed1993

Hydrogen peroxide stimulates sodium-potassium pump activity in cultured pulmonary arterial endothelial cells.

Oxidant injury to pulmonary vascular endothelium is an important factor in the pathogenesis of acute lung injury. Oxidant injury to other cell types has been reported to alter the function of Na-K-adenosinetriphophatase (ATPase) an enzyme important in maintenance of cellular ionic homeostasis and in transport of ions across biological membranes. We investigated the effect of H2O2 (0.001-10 mM) or xanthine (X) (15.2 micrograms/ml) plus xanthine oxidase (XO) (0.0153 U/ml) on the Na-K pump activity of cultured bovine pulmonary arterial endothelial cells (PAECs). We used a functional assay, using 86RbCl as a tracer for K+ and expressing Na-K pump activity as ouabain-inhibitable K+ uptake. Our results demonstrate that H2O2 and X/XO stimulate Na-K pump activity of bovine PAECs, an effect prevented by catalase. In addition, we assessed the affinity, number, and turnover of [3H]ouabain binding sites on intact endothelial monolayers and found that H2O2 increased affinity to [3H]ouabain, decreased the number of binding sites, and increased the rate of pump turnover. Influx of 22Na increased in response to a nonlytic concentration of H2O2. Cell injury, as assessed by 51Cr release, adherent cell number, and phase-microscopic morphology, was not observed after 30-min incubations with the lowest dose (1 mM) of H2O2 effective in stimulating Na-K pump activity, or after incubation with X/XO. Na-K pump inhibition by ouabain significantly increased the 51Cr release caused by H2O2 or by X/XO, suggesting that the increase in Na-K pump activity may be a compensatory response to the cellular alterations produced by H2O2. Incubation with H2O2 decreased cell ATP content, an effect which was not prevented by coincubation with ouabain. In summary, these results show that H2O2 increases Na-K pump activity of PAECs, an effect mediated, at least in part, by increased intracellular [Na] and by an increased rate of pump turnover. It is possible that the increased pump activity may be an early marker of endothelial cell perturbation.

Animals↗
PubMed1993

Characteristics of amphotericin B-induced endothelial cell injury.

The polyene antibiotic amphotericin B has been implicated in vascular injury in human subjects and lung injury in an animal model. Our objective was to determine whether amphotericin B directly injures endothelial cells and to investigate several possible mechanisms of injury. Confluent cultures of bovine endothelial cells were incubated with different concentrations of amphotericin B for varying time periods. Injury was assessed by using a chromium 51 release assay, adherent cell counts, and morphologic changes in the endothelial cell monolayers by phase microscopy. Amphotericin B increased 51Cr release in a dose- and time-dependent fashion. Corresponding to changes in 51Cr release, amphotericin B decreased adherent cell counts and disrupted the monolayers. Incubation with vehicle alone (sodium desoxycholate, 8.2 micrograms/ml) did not alter any of these parameters. Incubation of cells with a dose of antibiotic (1 micrograms/ml), which did not produce overt cell injury, significantly increased membrane permeability to K+ ions and activated the sodium/potassium adenosine triphosphatase (Na/K ATPase). Inhibition of the ATPase at this same antibiotic concentration (1 micrograms/ml) produced endothelial cell injury equivalent to the magnitude of injury observed with high doses of the antibiotic (10 micrograms/ml). In the presence of 10% fetal calf serum, the injury at 24 hours was significantly attenuated. This protective effect could not be attributed to binding of the drug by albumin because varying concentrations of bovine serum albumin in minimal essential medium without other serum constitutents had no effect on the magnitude of injury. Incubation of cells with several exogenous oxygen radical scavengers (dimethylthiourea, catalase, and mannitol) or a decrease in ambient oxygen tension during antibiotic exposure did not alter the magnitude of injury. The results demonstrate that amphotericin B directly injures endothelial cells in a dose- and time-dependent manner and demonstrate the importance of the Na/K ATPase for the maintenance of normal endothelial cell function and viability in response to this form of injury.

Amphotericin B↗
PubMed1992

Effects of hypoxia on heparan sulfate in bovine aortic and pulmonary artery endothelial cells.

Newly synthesized heparan sulfates purified from the cell layer of bovine aortic endothelial cells (BAECs) and main pulmonary artery endothelial cells (BPAECs) cultured under either normoxic (21% oxygen) or hypoxic (3% oxygen) conditions were characterized by size, charge, and capacity to bind to antithrombin III. Incorporation of radiolabeled sulfate into cell layer-associated heparan sulfate was reduced by 70% in BAECs and by 45% in BPAECs during exposure to 3% oxygen; degradation of radiolabeled heparan sulfate was not affected by hypoxia. However, the percentage of total radiolabeled heparan sulfate that bound to antithrombin III was increased by 33% for BAECs and by 120% for BPAECs when compared with radiolabeled heparan sulfate synthesized during the 21% oxygen exposure. Both the high- and low-antithrombin III affinity radiolabeled heparan sulfate consisted of two components of different sizes; the low-affinity components (mean sizes, 60 and 40 kd) generated under normoxic conditions were smaller than their respective high-affinity components (mean sizes, 70 and 55 kd) by molecular sieve chromatography. The components of low-antithrombin III affinity heparan sulfate generated during exposure to 3% oxygen were increased in size compared with the corresponding low-affinity components generated during the 21% oxygen exposure for both BPAECs and BAECs. In addition, the amount of the larger high-antithrombin III affinity component was reduced in both cell types exposed to hypoxia. There was no difference in functional heparin-like activity per dish between cells cultured at 3% and 21% oxygen; BAECs had twofold to threefold greater activity per dish than did BPAECs at both levels of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Neutrophil chemoattractant production by cultured serotonin-stimulated bovine and human endothelial cells.

Recent studies have demonstrated that serotonin (5-HT) is avidly taken up and metabolized by vascular endothelial cells (EC) and have suggested that 5-HT may contribute to inflammatory responses. Because EC can produce neutrophil cytokines among their biologically active molecules, we hypothesized that the interaction of 5-HT and EC might cause production of such a cytokine. Using a modified Boyden chamber assay, we found that cultured bovine aortic (BA), bovine pulmonary arterial (BPA), and human umbilical vein (HUV) EC incubated with 5-HT produced a neutrophil chemoattractant (NCA). The NCA was predominantly chemotactic, was not stored in an active form, appeared within 5 min of incubation with 5-HT, and required de novo protein synthesis for its appearance. The mechanism of NCA production was different in the three types of EC examined. Elaboration of NCA and BAEC and HUVEC was apparently mediated by 5-HT1 receptors and did not require uptake of 5-HT, whereas its elaboration from BPAEC required 5-HT uptake and was apparently mediated by 5-HT2 receptors. Incubation with three different lipoxygenase inhibitors blocked production of NCA, whereas incubation with a cyclooxygenase inhibitor did not. Further characterization of the NCA demonstrated that it was a mixture of several different chemotactic lipids and was distinct from other lipid or phospholipid neutrophil chemoattractants. These studies suggest that the interaction of the platelet-release product, 5-HT, with the adjacent endothelium results in the production of a chemoattractant that could affect neutrophil accumulation at sites of inflammation.

Animals↗
PubMed1991

Stimulation of fibroblast collagen and total protein formation by an endothelial cell-derived factor.

We investigated the effect of medium conditioned by bovine aortic endothelial cells on collagen accumulation and total protein formation by human embryonic fibroblasts or bovine smooth muscle cells in cultures. The conditioned medium at a 1:10 dilution induced a twofold increase in collagen and total protein accumulation in fibroblast cultures. At low concentration (1:50 dilution), the conditioned medium stimulated collagen accumulation preferentially; at high concentration (1:10 dilution), overall protein synthesis also was increased. The increase in type I collagen accumulation was associated with an increase in the steady-state level of alpha 1 (I) mRNA for collagen. The conditioned medium increased the production of types I and III collagen without affecting the proportion of collagen types in both fibroblast and smooth muscle cell cultures. Partial purification of the endothelial cell-derived factor disclosed it to be a heat-stable protein with an apparent molecular weight of 8-10 kDa. The stimulation of protein formation by this substance was not inhibited by antibodies against transforming growth factor-beta or the insulinlike growth factor I receptor. The partially purified factor stimulated protein production without affecting fibroblast proliferation. This endothelial cell-derived protein may play a role in the remodeling of vascular connective tissue by stimulating collagen synthesis.

Animals↗
PubMed1991

Primary pulmonary hypertension in the elderly.

Primary pulmonary hypertension is usually considered a disease of younger adults. We reviewed the natural course of primary pulmonary hypertension in patients aged 65 years or greater. During an 8-year period, 63 elderly patients were discharged from our hospital with a diagnosis of pulmonary hypertension. In eight instances, an elevated mean pulmonary arterial pressure (greater than 25 mm Hg) could not be explained by secondary causes. These elderly patients with primary pulmonary hypertension had symptoms common to younger patients with this disease, including dyspnea (eight patients), chest pain (five), pedal edema (four), and fatigue (one). In all but one patient, the initial diagnosis was incorrect, and the patients were thought to have more common diseases of the elderly that cause similar symptoms. Coexisting medical problems were common and further obscured the correct diagnosis. Survival was significantly shorter in those patients with symptoms of less than 6 months' duration. Primary pulmonary hypertension should be considered in the differential diagnosis in elderly patients with unexplained dyspnea and chest pain.

Aged↗
PubMed1990

Effect of long-term hypoxia on cultured aortic and pulmonary arterial endothelial cells.

In a previous study, we found a marked difference in the release of a cytokine, neutrophil chemoattractant activity (NCA), from cultured endothelial cells exposed to acute decreases in ambient oxygen, depending on the vascular bed of origin. In the current study, we used this cytokine to evaluate the effect of long-term exposure to decreased oxygen on endothelial cell function. We found that, in aortic and pulmonary arterial endothelial cells maintained for months in decreased ambient oxygen (10 or 3% oxygen), exposure to acute decreases in ambient oxygen caused a change in the pattern of NCA release; however, the differential response between the two cell types persisted. Aortic endothelial cells release NCA when exposed acutely to a level of oxygen below that in which they have been chronically maintained. In contrast, pulmonary arterial endothelial cells release NCA only when exposed to 0% oxygen acutely, but only if grown chronically in 10% oxygen; otherwise there was no release of NCA. As another indicator of endothelial cell function, we evaluated the effects of acute hypoxic exposure on prostacyclin production by endothelial cells maintained in 21 or 3% oxygen. If grown in 21% oxygen, both cell types decreased prostacyclin production upon exposure to 0% oxygen. However, when grown in 3% oxygen, only aortic endothelial cells decreased prostacyclin production when exposed acutely to 0% oxygen; pulmonary arterial endothelial cell prostacyclin production did not change. This study demonstrating the persistence of a differential pattern of NCA release and the appearance of a differential pattern of prostacyclin production after a long-term decrease in environmental oxygen suggests that the capacity of certain vascular endothelial cells to respond to decreases in oxygen concentration is carried by the cell throughout its existence. Thus, in certain situations, vascular endothelial cells may be important in sensing acute decreases in ambient oxygen.

Animals↗
PubMed1990

Pulmonary hypertensive response to foreign body microemboli.

Pulmonary hypertension and foreign body granulomas are recognized sequelae of chronic intravenous drug abuse. We have recently described the development of transient pulmonary hypertension and increased permeability pulmonary edema after the intravenous injection of crushed, suspended pentazocine tablets in both humans and dogs. To determine the role of vasoactive substances in the development of this transient pulmonary hypertension, we measured pulmonary hemodynamics and accumulation of arachidonic acid metabolites in dogs during the infusion of indomethacin, a cyclooxygenase inhibitor, diethylcarbamazine (DEC), a lipoxygenase inhibitor, and FPL 55712, a receptor antagonist for leukotriene C4/D4 (LTC4/D4). Following the intravenous administration of crushed, suspended pentazocine tablets (3-4 mg/kg of body weight), mean pulmonary artery pressure increased from 14 +/- 2 mmHg to 30 +/- 6 mmHg (p less than 0.05) at 60 secs with a concomitant increase in plasma concentrations of 6-keto-PGF1 alpha from 187 +/- 92 pg/ml to 732 +/- 104 pg/ml and thromboxane B2 from 206 +/- 83 pg/ml to 1362 +/- 117 pg/ml (both p less than 0.05). Indomethacin prevented the increase in both cyclooxygenase metabolites, but had no effect on the pulmonary hypertension. In contrast, DEC had no effect on the increase in cyclooxygenase products, but blocked the pulmonary hypertension. FPL 55712 did not effect either the increase in cyclooxygenase metabolites or the pulmonary hypertension. We conclude that the transient pulmonary hypertension, induced by the intravenous injection of crushed, suspended pentazocine tablets, is not mediated by cyclooxygenase products but may be mediated by lipoxygenase product(s) other than LTC4/D4.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Components of the angiotensin system cause release of a neutrophil chemoattractant from cultured bovine and human endothelial cells.

Evidence suggests that angiotensin II can affect macrophage-mediated inflammatory responses; however, whether it can affect neutrophil-mediated inflammatory responses is not yet clear. We have previously demonstrated that components of the angiotensin system simulate bovine aortic and human umbilical vein endothelial cells to release a neutrophil chemoattractant. In the current study, we examined the effect of components of the angiotensin system on bovine and human pulmonary arterial and human aortic endothelial cells, and partially characterized this neutrophil chemoattractant. All endothelial cell types incubated with angiotensin II released neutrophil chemoattractant activity. This activity appeared within 1 min of exposure to angiotensin II, and was blocked by saralasin, an angiotensin II antagonist. The neutrophil chemoattractant also appeared after exposure to angiotensin I, but this effect required conversion to angiotensin II. Incubation with bradykinin, another substrate for angiotensin-converting enzyme, did not cause release of the neutrophil chemoattractant. Chemoattractant release was not inhibited by indomethacin but was blocked by diethylcarbamazine or 5,8,11,14-eicosatetraynoic acid. Following extraction, the neutrophil chemoattractant partitioned completely into the organic phase. High-pressure liquid chromatography demonstrated several peaks of chemoactivity, none of which co-eluted with known eicosanoid or phospholipid neutrophil chemoattractants. This study demonstrates that angiotensin II may influence neutrophil accumulation via production of neutrophil chemoattractant activity by vascular endothelial cells.

Angiotensin I↗