Cyclooxygenase expression in canine platelets and Madin-Darby canine kidney cells.

OBJECTIVE: To examine cyclooxygenase (COX) expression in canine platelets and Madin-Darby canine kidney (MDCK) cells in culture. SAMPLE POPULATION: Canine platelets and MDCK cells. PROCEDURE: Total RNA was recovered from isolated canine platelets and MDCK cells. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR), using complementary DNA probes and primers designed from the human COX sequences, were used to determine COX-1 and -2 (cyclooxygenase isoforms 1 and 2) messenger RNA (mRNA) expression. RESULTS: Following northern blot analysis, canine platelets were found to express only the 2.8-kb COX-1 transcript; COX-2 was not detected. Canine MDCK cells expressed the 4.5-kb COX-2 transcript, in addition to the 2.8-kb COX-1 transcript. A single DNA band of 270 base pairs was identified following gel electrophoresis of the product obtained from RT-PCR of mRNA from canine platelets. Sequencing revealed that this PCR product was 90% homologous to a portion of the human COX-1 gene (Genbank M59979). CONCLUSIONS AND CLINICAL RELEVANCE: Detection of COX-1 by RT-PCR of RNA obtained from canine platelets is a novel finding. The 90% homology of the PCR product with the human sequence suggests strong conservation between the canine and human COX-1 gene. Cloning and sequencing of the canine gene will be required to fully characterize homologous regions. Because of the importance of COX in the inflammatory process and as a potential target of currently available nonsteroidal anti-inflammatory drugs (NSAID), a better understanding of canine COX may improve our ability to use NSAID appropriately, achieve efficacy, and avoid potential adverse drug effects in dogs.

In vitro allergen-induced degranulation of pulmonary mast cells from horses with recurrent airway obstruction (heaves).

OBJECTIVE: To determine the capacity of pulmonary mast cells (PMC) to degranulate in response to various potential allergens and other secretagogues in horses with recurrent airway obstruction (heaves) and clinically normal horses before and after exposure to moldy hay. ANIMALS: 5 horses with heaves and 5 clinically normal horses. PROCEDURES: Heaves was characterized as an increased clinical respiratory score and maximum change in transpulmonary pressure of > 20 cm H2O after exposure. Bronchoalveolar lavage was performed during each period. Washed and resuspended cells were exposed for 20 minutes at 37 C with whole reconstituted freeze-dried preparations of Aspergillus fumigatus, Alternaria tenuis, and Ambrosia elatior, fungal extracts of Aspergillus fumigatus, Alternaria tenuis, and Micropolyspora faeni; A23187; and compound 48/80. Histamine release (HR) was used as a marker of degranulation. RESULTS: Compared with clinically normal horses, HR was significantly greater from PMC from horses with heaves during remission and exacerbation in response to whole preparations and extracts of Aspergillus fumigatus and whole preparations of Alternaria tenuis. Extracts of Alternaria tenuis caused significantly greater HR from PMC from horses with heaves during exacerbation. Histamine was also released from PMC in response to A23187 and to changes in osmolality of the medium, but only as a result of cell lysis by compound 48/80. CONCLUSIONS: Increased degranulation of PMC after antigenic challenge may contribute to the pathogenesis of heaves in horses. CLINICAL RELEVANCE: Strategies for prevention and treatment that attenuate degranulation of PMC may assist in the clinical management of horses with heaves.

Cardiovascular effects of epidurally administered oxymorphone and an oxymorphone-bupivacaine combination in halothane-anesthetized dogs.

OBJECTIVE: To evaluate cardiovascular effects of epidurally administered oxymorphone (OXY) and an OXY-bupivacaine combination (O/B) in halothane-anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: In a randomized crossover design study, dogs were anesthetized with halothane and given OXY, O/B, and saline solution (SAL). Eucapnia and end-tidal halothane concentration of 1.2% were established. Heart rate (HR), systemic and pulmonary arterial pressures, central venous pressure (CVP), and cardiac output were measured at baseline and 5, 15, 30, 45, 60, and 75 minutes after treatment. At 90 minutes, glycopyrrolate was administered IV, and measurements were repeated at 95 minutes. Cardiac index (CI), stroke volume, stroke index, systemic vascular resistance (SVR), and left ventricular work were calculated. End-tidal halothane concentration was decreased to 0.8% from 17 to 45 minutes and to 0.5% from 47 to 95 minutes for OXY and O/B, whereas for SAL, it was maintained at 1.5 and 1.2%, respectively. Samples were obtained at 0, 2, 5, 15, 30, 45, 60, and 95 minutes for measurement of serum opiate concentration and comparison with values after IM administration of OXY. RESULTS: HR decreased, but CVP and SVR increased in response to OXY and O/B. These changes were reversed after IV administration of glycopyrrolate, resulting in significant increase in CI, compared with that in response to SAL. Serum opiate concentration increased markedly and peaked within 15 minutes after OXY and O/B administration but did not differ from values after IM administration. CONCLUSIONS: Epidural administration of OXY results in rapid systemic uptake and decreased HR. Glycopyrrolate administration improves HR, resulting in improved CI at equipotent halothane concentrations.

Efficacy of clomipramine in the treatment of canine compulsive disorder.

OBJECTIVE: To assess the efficacy of clomipramine for treatment of canine compulsive disorder (CCD). DESIGN: Randomized, placebo-controlled, double-blind, balanced AB-BA crossover clinical study. ANIMALS: 51 dogs with CCD. PROCEDURES: Dogs were given clomipramine (3 mg/kg [1.3 mg/lb] of body weight, PO, q 12 h) for 4 weeks and placebo for 4 weeks. At the end of each treatment each owner rated the severity of their dog's behavior, using 2 validated rating scales. Statistical analysis was made by ordinal regression. Compliance, adverse effects, and the effectiveness of masking were also assessed. Each dog's behavior was reevaluated 1 to 2 years after completing the study. RESULTS: Behaviors included spinning (n = 17) and self-mutilation by licking (acral lick dermatitis, 12). Both rating scales demonstrated a treatment effect. Compliance was satisfactory, and masking was effective. Sedation and reduced appetite were reported more commonly when dogs were given clomipramine than when they were given placebo. Forty-five dogs available for follow-up evaluation still had their behaviors; 6 dogs were lost to follow-up evaluation. CLINICAL IMPLICATIONS: Results suggest that clomipramine was effective in dogs with CCD and was not associated with serious adverse effects. However, treatment for 4 weeks was not curative. Behavior modification is likely to be necessary to manage CCD.

The pharmacokinetics of clomipramine and desmethylclomipramine in dogs: parameter estimates following a single oral dose and 28 consecutive daily oral doses of clomipramine.

Clomipramine is a tricyclic antidepressant that has been recommended for the treatment of canine compulsive disorder. The pharmacokinetics of clomipramine in dogs have not been reported. This study describes the pharmacokinetics of clomipramine and its active metabolite, desmethylclomipramine, in six male dogs. Serial blood samples were collected following both a single oral dose of clomipramine (3 mg/kg) and 28 consecutive daily oral doses (3 mg/kg q 24 h). In addition, 'peak' and 'trough' samples were taken throughout the 28-day dosing period. Plasma was assayed for total (free and protein-bound) clomipramine and desmethylclomipramine, using gas-chromatography with mass spectrometric detection. Various pharmacokinetic parameters were then determined. Following a single dose of clomipramine, time of maximum plasma concentration (tmax) of clomipramine was 0.75-3.1 h, maximum plasma concentration (Cmax) was 16-310 ng/mL and elimination half-life (t1/2el) was 1.2-16 h; tmax of desmethylclomipramine was 1.4-8.8 h, Cmax was 21-134 ng/ mL and t1/2el was 1.2-2.3 h. Following multiple dosing, there was a numeric increase in these parameters; tmax of clomipramine was 3-8 h, Cmax was 43-222 ng/mL and t1/2el was 1.2-16 h; tmax of desmethylclomipramine was 1.4-8.8 h, Cmax was 21-134 ng/mL and t1/2el was 1.2-2.3 h. Clinically significant differences between dogs and humans in the pharmacokinetics of oral clomipramine are discussed.

Evaluation of an in vitro degranulation challenge procedure for equine pulmonary mast cells.

Pulmonary mast cells (PMC) are important components of the inflammatory process in equine allergic lung diseases such as heaves. Very little, however, is known of the degranulation kinetics of these cells and thus, their pathophysiologic role remains largely speculative. The purpose of this study was to develop a repeatable protocol for in vitro equine PMC degranulation. Five mature horses (sex: 2 M, 3 F; age: 8.8 +/- 6.5 y), historically free of pulmonary disease and normal on clinical respiratory examination, arterial blood gas analysis, pulmonary mechanics testing and histamine inhalation challenge, were studied. Bronchoalveolar lavage was performed on 4 separate occasions, at least 2 d apart, in a different lung lobe on each occasion. The lavage fluid was concentrated by centrifugation. Cells were resuspended in modified HEPES/Tyrode, assessed for viability by Trypan blue exclusion, and PMC concentration determined. Cell inocula containing 30,000 PMC were incubated with 10(-8) to 6 x 10(-5) M A23187. Cells were then separated by centrifugation and histamine release (HR) was determined by fluorometric assay. The procedure was readily performed and yielded sufficient PMC for 30 to 60 inocula per lavage. Maximal HR (34.4 +/- 16.1%) was obtained with 10(-5) M A23187. The degranulation process was largely complete by 20 min but cell lysis was negligible. The challenge was repeatable within horse and produced a mean coefficient of variability of 23.0% following 20 min incubation with 10(-5) M A23187. We conclude that equine PMC degranulation can be repeatably performed in vitro and speculate that this protocol may be useful in further studies on the pathophysiology and treatment of equine allergic lung diseases.

The effect of the renal portal system on pharmacokinetic parameters in the red-eared slider (Trachemys scripta elegans).

The premise that drugs not be injected into the caudal body of reptiles because they will be carried by the renal portal system to the kidneys, where they may be nephrotoxic or rapidly excreted, was tested by comparing the pharmacokinetics of gentamicin (excreted via glomerular filtration in mammals) and carbenicillin (excreted partly via renal tubular secretion in mammals) following injection into the forelimb or hindlimb of red-eared sliders (Trachemys scripta elegans). Ten sliders received intramuscular gentamicin (10 mg/kg) in a forelimb (n = 5) or a hindlimb (n = 5), and plasma levels of the drug were assayed over time. Following drug clearance, the experiment was repeated with the site of injection reversed so that each animal acted as its own control. Another 10 sliders were similarly treated, using intramuscular carbenicillin (200 mg/kg). Injection site of gentamicin had no effect on any pharmacokinetic parameter (time to maximum plasma concentration, maximum plasma concentration, half-life, area under the curve, clearance, and volume of distribution). However, the area under the curve of plasma carbenicillin concentration vs. time was significantly lower following hindlimb injection, in comparison with forelimb injection, at 1, 4, and 8 hr, which may reflect reduced bioavailability of the drug, as would be expected with renal portal perfusion and tubular excretion on first pass through the kidney. This effect on carbenicillin likely is not clinically important because plasma levels remained above recommended minimum inhibitory concentrations. Because blood draining the caudal body of reptiles passes through the kidneys or the liver before reaching the central circulation, the effect on the pharmacokinetics of a drug injected in that region will vary with its renal or hepatic extraction rate. Generally, this effect is unlikely to be significant.

Development of a laboratory animal model of postoperative small intestinal adhesion formation in the rabbit.

In order to establish a model of postoperative intestinal adhesions that would simulate the problem experienced in horses, New Zealand White rabbits were utilized to compare two models of adhesion formation that had been successful in the horse, an ischemic strangulating obstruction (ISO) model and a serosal scarification model. An untreated control group was compared with animals subjected to 1, 2, 3 and 4 h periods of ISO, and to serosal scarification. At postmortem examination 14 d postoperatively, the number of rabbits in each group with adhesions was recorded. Serosal scarification was significantly more consistent at producing adhesions than ISO (Fisher's exact test, P = 0.0022). The 3 h of ISO group was significantly different from the control group: however, compared to the serosal scarification group, fewer animals had adhesions and one animal died of complications associated with the experimental procedure. Based on these results, serosal scarification was selected as the best model for utilization in further studies of adhesion prevention.

Utilization of the serosal scarification model of postoperative intestinal adhesion formation to investigate potential adhesion-preventing substances in the rabbit.

A rabbit serosal scarification model was utilized to compare the ability of four drugs, previously administered peri-operatively to horses undergoing exploratory celiotomy, to prevent the development of postoperative intestinal adhesions. The substances compared were 32% Dextran 70 (7 mL/kg), 1% sodium carboxymethylcellulose (7 mL/kg), trimethoprim-sulfadiazine (30 mg/kg), and flunixin meglumine (1 mg/kg). The first two were administered intra-abdominally following surgery, while the latter two were administered systemically in the peri-operative period. Fibrous adhesions were evident in all animals in the untreated serosal scarification group. No significant difference in the number of animals with adhesions was found between the untreated control group and any treatment group, nor among the treatment groups. Microscopic examination of adhesions collected at postmortem examination revealed fibers consistent with cotton, surrounded by a giant-cell reaction and ongoing acute inflammation. The source of the fibers was likely the cotton laparotomy sponges used to scarify the intestinal surface, since the pattern in the granuloma and sponge fibers appeared similar under polarized light. Though consistent intestinal adhesion formation was produced in the rabbit, the presence of foreign body granulomas may prevent consideration of this model for future research. The drugs tested were ineffective in preventing the formation of postoperative small intestinal adhesions in this model.

Ozone-induced oxygen radical release from bronchoalveolar lavage cells and airway hyper-responsiveness in dogs.

1. Ozone inhalation causes airway hyper-responsiveness and airway inflammation in dogs. The purpose of this study was to determine whether these effects are associated with increases in oxygen radical production from bronchoalveolar lavage (BAL) cells. 2. Twelve randomly selected dogs were studied twice, 4 weeks apart. On each study day, acetylcholine (ACh) airway responsiveness was measured before and 1 h after ozone (3 p.p.m., 30 min) or dry air inhalation, followed by BAL. The response to ACh was expressed as the concentration causing an increase in lung resistance of 5 cmH2O l-1 s-1 above baseline. Spontaneous and phorbol myristate acetate (PMA) (2.4 mumol l-1)-stimulated oxygen radical release from washed BAL cells (4 x 10(6) cells ml-1) was measured by luminol-enhanced chemiluminescence in a luminometer at 37 degrees C. 3. Ozone inhalation caused airway hyper-responsiveness. The concentration of ACh causing an increase in lung resistance of 5 cmH2O l-1 s-1 (the 'provocative' concentration) fell from 4.68 mg ml-1 (% S.E.M., 1.43) before, to 0.48 mg ml-1 (% S.E.M., 1.60) after ozone (P < 0.0001). Spontaneous chemiluminescence area under the curve (AUC) significantly increased after ozone from 4.08 mV (10 min) (% S.E.M., 1.28) after dry air to 8.25 mV (10 min; % S.E.M., 1.29) after ozone (P = 0.007). Ozone inhalation also increased PMA-stimulated chemiluminescence AUC from 18.97 mV (10 min; % S.E.M., 1.18) after dry air to 144.03 mV (10 min; % S.E.M., 1.45) after ozone (P = 0.0001). The increase in PMA-stimulated chemiluminescence was significantly correlated with ozone-induced ACh airway hyper-responsiveness (r = 0.83, P < 0.001). 4. These results indicate that inhaled ozone increases oxygen radical release from BAL cells and suggest that oxygen radicals are important in causing ozone-induced airway hyper-responsiveness.

Effect of sodium cromoglycate on light racehorses with elevated metachromatic cell numbers on bronchoalveolar lavage and reduced exercise tolerance.

Some young horses with clinical signs of small airway disease demonstrate increased metachromatic cell numbers on bronchoalveolar lavage. The purpose of this study was to determine the effect of sodium cromoglycate treatment on clinical signs, bronchoalveolar lavage cytology and bronchoalveolar lavage histamine parameters in these horses. Twelve racehorses (age: 3.4 +/- 1.6 years) with a history of respiratory embarrassment at exercise, clinical signs of obstructive airway disease and bronchoalveolar lavage metachromatic cell differential greater than 2% were selected. Horses were randomly assigned to receive either 200 mg sodium cromoglycate or saline placebo nebulized twice daily for 7 days. A clinical respiratory score was assigned and bronchoalveolar lavage was performed on each animal on days 0 and 7. Measurements were made of the following bronchoalveolar lavage fluid parameters: total nucleated cell concentration, differential cell percentage and concentration, supernatant and lysate histamine concentration, lysate: supernatant histamine ratio and metachromatic cell histamine content. Between the two evaluation periods, sodium cromoglycate treated horses demonstrated an improvement in respiratory score (P = 0.01) and a stabilizing of metachromatic cell histamine content (P = 0.04) when compared with placebo treated horses. We concluded that sodium cromoglycate is effective for the treatment of small airway disease in this population of young racehorses although the pharmacodynamics of this drug in the horse require further investigation.

Pasteurella haemolytica leukotoxin induces histamine release from bovine pulmonary mast cells.

Pasteurella haemolytica A1 leukotoxic culture supernatant was evaluated for its ability to induce histamine release from bovine pulmonary mast cells isolated by enzymatic dispersion of lung tissue. Histamine was measured by a radioimmunoassay technique. Leukotoxic culture supernatant of P. haemolytica significantly released histamine in a time and concentration-related manner. This effect was lost when culture supernatant was heat-inactivated or preincubated with leukotoxin neutralizing rabbit serum. Preincubation of the mast cells with propranolol or p-bromophenacyl bromide reduced the histamine-releasing effect of leukotoxin, while verapamil enhanced release. Experimental infection of calves with P. haemolytica A1 reduced the total histamine content of pulmonary mast cells recovered at postmortem. Histamine release induced by P. haemolytica leukotoxin is likely an important factor in the pathogenesis of bovine pneumonic pasteurellosis.

Evaluation of route and frequency of administration of three antimicrobial drugs in cattle.

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 mug/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 mug/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 mug/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 mug/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean +/- SD concentrations (mug/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 +/- 1.27 (injection site), 1.00 +/- 0.80 (liver), 0.90 +/- 0.58 (renal cortex), 0,58 +/- 0.17 (renal medulla), 0.13 +/- 0.11 (diaphragm), 0.10 +/- 0.08 (gluteal muscle), and 0.06 +/- 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days.

Clinical pharmacokinetics of amikacin in hypoxic premature foals.

The pharmacokinetics of amikacin, administered iv at 7 mg/kg, every 8 h, were evaluated over the first 48 h of hospitalisation in 7 critically ill hypoxic premature foals and compared with those in 8 full-term nonhypoxic critically ill neonatal foals. The pharmacokinetic data were used to calculate dosage schedules that would maintain the plasma amikacin concentrations in individual foals within a target range of > or = 15 micrograms/ml but < 30 micrograms/ml for peak values and < or = 3 micrograms/ml for trough values. The results indicated a statistically significant increase in the amikacin serum half-life (5.39 +/- 3.46 h) and smaller elimination rate constant (0.17 +/- 0.09 h-1) in premature foals. The pharmacokinetic derangements required increasing the dose to 8.5-10.5 mg/kg bwt in 6 of 7 premature foals and an increase in the dosage interval to 12-24 h in all 7 foals. Overall, the total dosage of amikacin was decreased in the hypoxic, premature foals so that target peaks and troughs could be maintained. Our findings suggest that prematurity and hypoxia are variables related to a prolonged serum half-life of amikacin in hypoxic, premature foals. Although there was no evidence of amikacin-induced nephrotoxicity in any of these foals, daily monitoring and tailoring of the dose schedule to the individual foal are strongly advised.

Effects of hypoxia and azotaemia on the pharmacokinetics of amikacin in neonatal foals.

The effects of hypoxia and azotaemia on the pharmacokinetics of amikacin were evaluated in 20 full-term neonatal critically ill foals which required 24-h supportive care, antibiotics and dextrose-supplemented polyionic fluids given intravenously, nasal insufflation with oxygen and nutritional supplementation. There was no association between sepsis score or survival and pharmacokinetic parameters. Concurrent hypoxia and azotaemia were associated with significantly decreased clearance and increased peak and trough serum concentrations of amikacin; however, peaks or troughs did not exceed toxic values. Derangements in serum peak, trough and clearance values, which were present on admission, persisted over the 6-day duration of this study. Daily monitoring of serum amikacin concentration revealed a tendency to underdose (particularly in foals receiving aggressive fluid therapy), which necessitated increasing the dose/kg body weight (9-12 mg/kg) and increasing the dose interval (10-12 h) in 40% (8/20) of the cases, so that blood concentrations of amikacin could be maintained within the target range of 3-15 micrograms/ml. Amikacin-induced nephrotoxicity was not indicated by conventional laboratory testing, nor was it strongly suspected after examination of post mortem lesions.

Bovine platelets retain functional activity in the presence of penicillin G.

It has been reported that antibiotics of the penicillin family impair the functional response of human, canine and lapine platelets to a broad range of agonists. In contrast, we have shown that the bovine platelet retained full functional responses to stimulation by adenosine diphosphate (ADP) or platelet activating factor (PAF) following administration of penicillin G to clinically normal cattle at 20,000 IU/kg for three days. The aggregation response to collagen was transiently reduced to approximately 50% of pretreatment values, but only while the drug was detectable in the circulation. When penicillin was added to platelet rich plasma suspensions, ADP-induced aggregation was similar to that of the control untreated platelets, while the PAF-induced aggregation response was reduced by not more than 25%. Only collagen-induced aggregation exhibited a modest dose-dependent inhibitory response in the presence of penicillin. It is postulated that the relative insensitivity of the bovine platelet to penicillin may be related to differences in postreceptor biochemical events compared to the human platelet.

Antimicrobial drugs for respiratory tract infections.

The respiratory tract of small animals is exposed to a large number of potential pathogens. If endogenous defense mechanisms are not able to remove the invading microorganism, infection may result. The veterinarian must then determine if antimicrobial therapy is appropriate and, if so, which drug to use, at which dose, and for how long. This article discusses the therapeutic problems that arise when deciding on antimicrobial therapy in small animal respiratory disease.

Effects of Pasteurella haemolytica A1 culture supernatant on mechanisms controlling bovine alveolar macrophage oxygen radical production.

Pasteurella haemolytica A1 culture supernatant containing leukotoxin, and modifiers of cyclic nucleotide and arachidonate metabolism, were evaluated for their ability to alter oxygen radical production by pulmonary alveolar macrophages obtained from seven Holstein calves. Calves were sedated, and underwent bronchoalveolar lavage to harvest macrophages, which were then incubated with culture supernatant and/or the drugs and toxins under study, and challenged with opsonized zymosan to induce oxygen radical generation. This was measured by a chemiluminescence technique. Pasteurella haemolytica A1 culture supernatant alone delayed the time to maximum oxygen radical production, although total production was increased. The cyclooxygenase inhibitor indomethacin and the phospholipase inhibitor p-bromophenacyl bromide significantly reduced maximum oxygen radical production, but their effects were diminished in the presence of culture supernatant. Although forskolin markedly inhibited oxygen radical generation, this effect was not altered by culture supernatant. Incubation of macrophages with pertussis toxin had no effect on oxygen radical production, while incubation with cholera toxin did inhibit production. This inhibitory effect was significantly lessened by concurrent incubation with P. haemolytica A1 culture supernatant.

Beta-adrenergic receptor function and oxygen radical production in bovine pulmonary alveolar macrophages.

Reactive oxygen species production by bovine pulmonary alveolar macrophages was evaluated by a chemiluminescence assay utilizing luminol and opsonized zymosan. Incubation with dobutamine (5 x 10(-8) and 5 x 10(-7) M) or isoproterenol (5 x 10(-8) and 5 x 10(-7) M) prior to zymosan challenge significantly (p less than 0.05) increased the time for chemiluminescence to begin, and significantly decreased the level of maximum chemiluminescence. The agonists' inhibitory effects on maximum chemiluminescence were significantly reduced by pre-incubation with the appropriate antagonist (atenolol at 1 x 10(-6) M for dobutamine; and propranolol at 1 x 10(-6) M for isoproterenol). Salbutamol at 1 x 10(-6) M significantly reduced the level of maximum chemiluminescence only, but did not increase the time for chemiluminescence to begin. This effect was significantly reduced by the presence of the beta 2-antagonist ICI 118,551 at 1 x 10(-6) M. The results reveal the presence of beta 1- and beta 2-adrenoceptors on bovine pulmonary alveolar macrophages, and suggest that these receptors are important in the regulation of reactive oxygen species production by these cells.