Changes in the blood redox status of horses subjected to combat training.

Combat training of police horses, involving physical activity in the presence of environmental stressors, poses a risk of oxidative stress. This study compared the oxidative imbalance after combat training in horses in the regular police service and in horses that had just been schooled. Blood collection was performed immediately after training and after 16 h rest. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total antioxidant status (TAS) were determined as the markers of enzymatic antioxidant defence. At the same time, lipid peroxidation (TBARS) and protein carbonylation (Carb) were assessed as oxidation biomarkers. Additionally, oxidative imbalance indexes such as SOD/CAT, SOD/GPx, TBARS/TAS and TBARS/GPx were calculated. Animals during schooling had significantly lower SOD activity in erythrocytes than those experienced. CAT activity in erythrocytes was insignificantly higher immediately after training than during recovery. The SOD/GPx ratio was higher in experienced animals, which may reflect the intra-erythrocyte imbalance between enzymes producing and degrading hydrogen peroxide towards the first one. The concentration of carbonyl groups was significantly higher after the combat training compared to the recovery period in all horses. In inexperienced animals slight increase in TBARS/TAS and TBARS/GPx indexes were observed during the recovery time after exercises, contrary to experienced horses, in which these markers decreased slightly. These results suggest that the oxidative imbalance in inexperienced horses, although less pronounced just after combat training, was more prolonged as compared to horses in regular service.

Evaluation of selected hematological, biochemical and oxidative stress parameters in stored canine CPDA-1 whole blood.

Blood transfusions are mainly given to intensive care patients; therefore, additional complications that could arise from storage lesions in preserved blood should be avoided. It has been shown that human stored red blood cells are subject to changes that are considered to be a number of interdependent processes involving metabolic disarrangement and oxidative stress. The aim of our study was to determine alterations in selected hematological and biochemical parameters and to assess whether and when oxidative stress is a significant phenomenon in stored dog CPDA-1 whole blood. Ten ½ unit bags of whole blood donated from dogs and preserved with CPDA-1 (anticoagulant containing citrate, phosphate, dextrose and adenine) were stored for 5 weeks. Each week, a 9 ml sample was drawn aseptically to measure hematological parameters, selected metabolites, free hemoglobin content, osmotic fragility, antioxidant enzyme activity, total antioxidant capacity, malondialdehyde concentration and protein carbonyl content.The results revealed an MCV decrease in the first week of storage and then a gradual increase; osmotic fragility decreased at that time and remained low throughout the study period. Leukodepletion became significant in the fourth week of storage. The free hemoglobin concentration continuously increased, with the greatest changes observed in the last two weeks of storage. The total antioxidant capacity changed in a reverse manner. Superoxide dismutase and glutathione peroxidase activities decreased from week 0 to week 3, and catalase activity tended to decrease over time. The highest malondialdehyde concentrations in blood supernatant were measured in the first week of storage, and the carbonyl concentration increased after 35 days.Hematological changes and oxidative stress are already present in the first week of storage, resulting in depletion of the antioxidant system and subsequent accumulation of oxidation products as well as erythrocyte hemolysis, which are most pronounced at the end of the storage period.

Local Effects of a 1940 nm Thulium-Doped Fiber Laser and a 1470 nm Diode Laser on the Pulmonary Parenchyma: An Experimental Study in a Pig Model.

The lungs are a common site of metastases from malignant tumors. Their removal with a minimal but safe tissue margin is essential for the long-term survival of patients. The aim of this study was to evaluate the usefulness of a 1940 nm thulium-doped fiber laser (TDFL) and a 1470 nm diode laser (DL) in a pig model of lung surgery that involved the incision and excision of lung tissue. Histopathological analysis was performed on days 0 and 7 after surgery. Neither TDFL nor DL caused significant perioperative or postoperative bleeding. Histological analysis revealed the presence of carbonized necrotic tissue, mixed fibrin-cellular exudate in the superficial zone of thermal damage and bands of deeper thermal changes. The mean total width of thermal damage on day 0 was 499.46 ± 61.44 and 937.39 ± 109.65 µm for TDFL and DL, respectively. On day 7, cell activation and repair processes were visible. The total width of thermal damage was 2615.74 ± 487.17 µm for TDFL vs. 6500.34 ±1118.02 µm for DL. The superficial zone of thermal damage was narrower for TDFL on both days 0 and 7. The results confirm the effectiveness of both types of laser in cutting and providing hemostasis in the lungs. TDFL caused less thermal damage to the lung parenchyma than DL.

Atherosclerosis Development and Aortic Contractility in Hypercholesterolemic Rabbits Supplemented with Two Different Flaxseed Varieties.

Alpha-linolenic acid (ALA) is widely regarded as the main beneficial component of flax for the prevention of cardiovascular disease. We evaluated the effect of the transgenic flaxseed W86-which is rich in ALA-on the lipid profile, atherosclerosis progression, and vascular reactivity in hypercholesterolemic rabbits compared to the parental cultivar Linola with a very low ALA content. Rabbits were fed a basal diet (control) or a basal diet supplemented with 1% cholesterol, 1% cholesterol and 10% flaxseed W86, or 1% cholesterol and 10% Linola flaxseed. A high-cholesterol diet resulted in an elevated plasma cholesterol and triglyceride levels compared to the control animals. Aortic sections from rabbits fed Linola had lower deposits of foamy cells than those from rabbits fed W86. A potassium-induced and phenylephrine-induced contractile response was enhanced by a high-cholesterol diet and not influenced by the W86 or Linola flaxseed. Pretreatment of the aortic rings with nitro-L-arginine methyl ester resulted in a concentration-dependent tendency to increase the reaction amplitude in the control and high-cholesterol diet groups but not the flaxseed groups. Linola flaxseed with a low ALA content more effectively reduced the atherosclerosis progression compared with the W86 flaxseed with a high concentration of stable ALA. Aorta contractility studies suggested that flaxseed ameliorated an increased contractility in hypercholesterolemia but had little or no impact on NO synthesis in the vascular wall.

Usefulness of Thulium-Doped Fiber Laser and Diode Laser in Zero Ischemia Kidney Surgery-Comparative Study in Pig Model.

BACKGROUND: The aim of this study was to evaluate the usefulness of a thulium-doped fiber laser and a diode laser in zero ischemia kidney surgery, by carrying out a comparative study in a pig model. MATERIAL AND METHODS: Research was carried out on 12 pigs weighing 30 kg each. A thulium-doped fiber laser (TDFL) and a diode laser (DL) operating at wavelengths of 1940 and 1470 nm, respectively, were used. The cut sites were assessed both macroscopically and microscopically. The zone of thermal damage visible in the histopathological preparations was divided into superficial and total areas. RESULTS: During partial nephrectomy, moderate to minimal bleeding was observed, which did not require additional hemostatic measures. All animals survived the procedure. On day 0, the total thermal damage depth was 837.8 µm for the TDFL and 1175.0 µm for the DL. On day 7, the depths were 1556.2 and 2301.7 µm, respectively. On day 14, the overall thermal damage depth for the DL was the greatest (6800 µm). The width of the superficial zone was significantly reduced on days 7 and 14 after TDFL application. CONCLUSION: Both lasers are suitable for partial wedge nephrectomy without ischemia in pigs. The TDFL produced similar or better hemostasis than the DL, with a smaller zone of thermal damage and, therefore, seems more suitable for application in human medicine.

Maintaining Optimal Mammary Gland Health and Prevention of Mastitis.

In dairy industry, quality of produced milk must be more important than quantity without a high somatic cells count (SCC) or pathogens causing mastitis of dairy cows and consumer diseases. Preserving the good health of dairy cows is a daily challenge for all involved in primary milk production. Despite the increasing level of technological support and veterinary measures, inflammation of the mammary gland-mastitis, is still one of the main health problems and reasons for economic losses faced by cow farmers. The mammary gland of high-yielding dairy cows requires making the right decisions and enforcing the proper measures aimed at minimizing external and internal factors that increase the risk of intramammary infection. Due to the polyfactorial nature of mastitis related to its reduction, the effectiveness of commonly used antimastitis methods tends to be limited and therefore it is necessary to find the areas of risk in udder health programs and monitoring systems. Only by implementing of complete udder health programs should be accompanied by research efforts to further development these complete udder health control. The present review analyses the current knowledge dealing with damping and prevention of mastitis include SCC control, proper nutrition, housing and management, milking and drying as practiced in dairy farming conditions. This information may help to improve the health of the mammary gland and the welfare of the dairy cows as well as the production of safe milk for consumers.

Comparison of A 1940 nm Thulium-Doped Fiber Laser and A 1470 nm Diode Laser for Cutting Efficacy and Hemostasis in A Pig Model of Spleen Surgery.

Partial and total splenectomies are associated with a high risk of substantial blood loss. Lasers operating at wavelengths strongly absorbed by water have the potential to improve hemostasis and cut while providing a narrow zone of thermal damage. The aim of this study is to compare a thulium-doped fiber laser (TDFL) emitting a wavelength of 1940 nm and a diode laser (DL) operating at 1470 nm for spleen surgery in a pig model. A partial splenectomy and spleen incisions were made in 12 animals using the two laser devices. The hemostasis was evaluated visually during surgeries. Post-mortem and histopathological evaluations were done on days 0, 7, and 14 following surgery. Neither TDFL nor DL caused bleeding on day 0 or delayed bleeding. On day 14, pale streaks at the site of incision were slightly wider after cutting with DL than with TDFL. Histological analysis revealed a carbonized zone with exudation and a deeper zone of thermal tissue damage on day 0. The width of the thermal changes was 655.26 ± 107.70 µm for TDFL and 1413.37 ± 111.85 µm for DL. On day 7, a proliferation of fibroblasts and splenocytes was visible, as well as a formation of multinucleated giant cells adjacent to the residues of carbonization. The zone of thermal damage was broader for DL (1157.5 ± 262.77 µm) than for TDFL (682.22 ± 116.58 µm). On day 14, cutting sites were filled with connective and granulation tissues with the residues of carbonization. The zone of thermal damage was narrower for TDFL (761.65 ± 34.3 µm) than for DL (1609.82 ± 202.22 µm). Thus, both lasers are efficient in spleen surgery, providing good hemostasis. However, TDFL produces a narrower zone of thermal damage, which suggests its better efficiency for spleen surgery, especially when performing more precise procedures.

Aging Markers in Equine Red Blood Cells.

Detection of hematopoietic activity in horses is a challenge due to the lack of cells carrying reticulocyte markers such as RNA remnants or CD71 in the circulation. In this study, we fractionated equine red cells according to their density and analyzed the cells forming low (L), medium (M), and high (H) density fractions for markers of aging such as membrane loss, oxidation, and alterations in the intracellular free Ca2+ levels. Cells forming L and M fraction were highly heterogeneous in projected areas and shapes, and had higher propensity to swell in response to hypo-osmotic challenge than the cells from the H fraction. The densest cells were deprived of band 3 protein compared to the cells within L or M fraction. Furthermore, the equine red cells from the H fraction were hyper-oxidized compared to the cells within M and L fractions as follows from an increase in autofluorescence characteristic for oxidized damaged hemoglobin and from thiol oxidation as detected using monobromobimane. The lightest cells showed lower free thiol content compared to the red blood cells from the M fraction, but did not contain oxidized hemoglobin. Finally, the majority of red blood cells forming L, M, and H fraction prominently differed from each other in intracellular free Ca2+ levels and its distribution within the cells. Based on the obtained findings, we suggest that intraerythrocytic Ca2+ levels and its subcellular distribution, eosin-5-maleimide binding test for band 3 abundance, and autofluorescence of cells along with the changes in red blood cell indices, distribution width and creatine levels may become potential markers of regenerative erythropoiesis in horses. Validation of the power of these potential markers of red cell aging is pending.

Applicability of FTIR-ATR Method to Measure Carbonyls in Blood Plasma after Physical and Mental Stress.

INTRODUCTION: Oxidative stress is a state of imbalance between the production of reactive oxygen species and antioxidant defenses. It results in the oxidation of all cellular elements and, to a large extent, proteins, causing inter alia the formation of carbonyl groups in their structures. The study focused on assessment of changes in the plasma protein-bound carbonyls in police horses after combat training and after rest and the applicability of infrared spectroscopy with a Fourier transform, utilizing the attenuated total reflectance (FTIR-ATR) in detecting plasma protein oxidation. METHODS: We evaluated the influence of both the different concentrations of hydrogen peroxide and combat training on protein carbonylation in horse blood plasma. The oxidation of plasma proteins was assessed using a spectrophotometric method based on the carbonyl groups derivatization with 2,4-dinitrophenylhydrazine (DNPH). The measured values were correlated with the carbonyl groups concentrations determined by means of the FTIR-ATR method. RESULTS: The linear correlation between the DNPH and FTIR-ATR methods was shown. The concentration of plasma protein-bound carbonyls significantly deceased in police horses after one-day rest when compared to the values measured directly after the combat training (a drop by 23%, p<0.05 and 29%, p<0.01 measured by DNPH and FTIR-ATR methods, respectively). These results were consistent with the proteins phosphorylation analysis. CONCLUSION: The FTIR-ATR method may be applied to measure the level of plasma proteins peroxidation.

Publisher Correction: Low-level light therapy reduces platelet destruction during extracorporeal circulation.

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Low-level light therapy reduces platelet destruction during extracorporeal circulation.

Extracorporeal circulation causes many deleterious effects on blood cells. Low-level light therapy (LLLT) in the red/near-infrared spectral range is known for its cytoprotective properties but its use during cardiopulmonary bypass (CPB) has not yet been studied. We aimed to assess whether LLLT protects platelets during CPB. 24 pigs were connected to 1-hour-CPB and observed for the next 23 hours. In 12 animals, blood circulating through the oxygenator was treated with LLLT. Platelet count and function were monitored throughout the experiment. The decrease in platelet count was greater in the control group, especially during CPB and after 24 hours. In LLLT group CD62P expression remained quite stable up to the 12th hour of the experiment, whereas in the control group it continuously decreased till the end of observation. Platelets in the control group were more prone to aggregation in the postoperative period than at the beginning of the experiment, whereas platelets in the LLLT group aggregated similarly or less intense. Limitation of platelet loss, pattern of aggregation and CD62P expression suggest that LLLT may stabilize platelet function during CPB and diminish the negative effects associated with the interaction of cells with an artificial surface.

Preliminary Evaluation of Thulium Doped Fiber Laser in Pig Model of Liver Surgery.

Partial liver resection is a treatment of choice for liver tumors; the range of parenchyma excision varies from a small part of the tissue surrounding the neoplasm up to 70% of the organ. One of the major concerns during liver resection is blood loss. Thulium lasers which are characterized by the length of emission wave corresponding to a peak absorption of water create a new possibility of cutting tissues efficiently with minimal thermal damage and concurrently providing a good hemostasis control. The aim of our study was to evaluate an impact of liver transection with thulium doped fiber laser on an intraoperative bleeding and histopathological changes during postoperative period in swine model. Ten animals were subjected to open surgery partial liver resection and an incision of liver tissue with an all-fiber, diode-pumped, and continuous-wave Tm3+-doped fiber laser emitting 37.4 W of output power at ~1.94 µm wavelength. The macroscopic and histopathological evaluation was performed intraoperatively as well as 7 and 14 days after surgery. Macroscopically almost no bleeding was observed during surgery and no signs of bleeding were stated after 7 and 14 days. Histopathological analysis of the transection margin revealed a thermal damage area ranging in depth from 620.23 ± 23.82 µm on the day of surgery to 1817.70 ± 211.98 µm after 7 days. In the samples taken intraoperatively and after 7 days a superficial zone of carbonization was visibly separated from the deeper changes. After 14 days one 765.35 µm deep zone characterized by a granulation was present. In conclusion, thulium doped fiber laser is efficacious in cutting with a narrow zone of thermal injury and provides a good hemostasis during liver transection, thus being a potential tool for oncotic liver surgery.

Low-Level Light Therapy Protects Red Blood Cells Against Oxidative Stress and Hemolysis During Extracorporeal Circulation.

Aim: An activation of non-specific inflammatory response, coagulation disorder, and blood morphotic elements damage are the main side effects of the extracorporeal circulation (ECC). Red-to-near-infrared radiation (R/NIR) is thought to be capable of stabilizing red blood cell (RBC) membrane through increasing its resistance to destructive factors. We focused on the development of a method using low-level light therapy (LLLT) in the spectral range of R/NIR which could reduce blood trauma caused by the heart-lung machine during surgery. Methods: R/NIR emitter was adjusted in terms of geometry and optics to ECC circuit. The method of extracorporeal blood photobiomodulation was tested during in vivo experiments in an animal, porcine model (1 h of ECC plus 23 h of animal observation). A total of 24 sows weighing 90-100 kg were divided into two equal groups: control one and LLLT. Blood samples were taken during the experiment to determine changes in blood morphology [RBC and white blood cell (WBC) counts, hemoglobin (Hgb)], indicators of hemolysis [plasma-free hemoglobin (PFHgb), serum bilirubin concentration, serum lactate dehydrogenase (LDH) activity], and oxidative stress markers [thiobarbituric acid reactive substances (TBARS) concentration, total antioxidant capacity (TAC)]. Results: In the control group, a rapid systemic decrease in WBC count during ECC was accompanied by a significant increase in RBC membrane lipids peroxidation, while in the LLLT group the number of WBC and TBARS concentration both remained relatively constant, indicating limitation of the inflammatory process. These results were consistent with the change in the hemolysis markers like PFHgb, LDH, and serum bilirubin concentration, which were significantly reduced in LLLT group. No differences in TAC, RBC count, and Hgb concentration were detected. Conclusion: We presented the applicability of the LLLT with R/NIR radiation to blood trauma reduction during ECC.

Sheep model of haemodialysis treatment.

More than two million patients received haemodialysis (HD) in 2013. Many methods for improving dialysis therapy outcomes have been tested. Nevertheless, patients continue to experience high morbidity and mortality rates. We aimed to develop an animal model of HD treatment to study methods that would prevent the adverse effects of renal replacement therapy. The study was conducted using six male Merino sheep. The animals underwent a two-step bilateral nephrectomy, and a permanent dual-lumen catheter was inserted into the jugular vein. In each animal, 10 short, daily HD treatments were conducted. The dialysis prescription was adjusted individually to each animal. Measures of dialysis adequacy (spKt/V and urea reduction ratio [URR]) were calculated for each HD treatment. All animals remained in a good clinical state during the experiment. However, a sustained decrease in red blood cell count was detected. The average URR was 0.65 ± 0.01, whereas the calculated spKt/V was approximately 1.16 ± 0.03. Neither hyperphosphataemia nor a significant decline in serum albumin concentrations were detected during the study. A sustained increase in serum potassium concentrations was detected on consecutive days of the experiment. All sheep survived the treatment and were euthanized at the end of the experiment. In conclusion, we developed a reproducible sheep model of HD treatment. The gentle nature and specific anatomical features of sheep provided easy blood access and allowed us to perform HD without pharmacological intervention. However, some differences in sheep physiology relative to human physiology must be considered when interpreting the results of the study.

In Vitro Study of Caecal and Colon Microbial Fermentation Patterns in Wild Boar (Sus scrofa scrofa).

The aim of this study was to evaluate wild boar (Sus scrofa scrofa) caecal and colon products of microbial activity including short chain fatty acids (SCFA), ammonia and methane concentrations. The in vitro method was applied to caecal and colon contents after 12 and 24-hour incubation with the substrate (wheat bran), or without any additive (control samples). The pH was also measured in each sample. In samples incubated with the substrate, a lower pH was noted as compared to the control (P < 0.001). In terms of the total SCFA concentration, the hindgut microbial fermentation pattern of wild boar was characterized by a high acetate level, followed by propionate and then butyrate at a ratio of 7:1.5:1. Substrate addition decreased acetate molar proportions (P < 0.001) and increased those of butyrate (P < 0.001) as well as propionate (P < 0.05). The total SCFA level in fresh, unincubated caecal samples (128 mmol/kg) was similar to that in the colon (111 mmol/kg). The ammonia concentrations were at the level of 0.8-1.5 mmol/kg of hindgut content and did not differ between the two investigated hindgut parts. Methanogenesis was also similar in the caecum and colon and after 24h was 2.69 mmol/kg and 2.27 for caecal colon control samples, respectively. The substrate increased total gas production and methane concentration (P < 0.001).

Influence of ovariohysterectomy and deslorelin acetate on the spontaneous activity of the rabbit urinary bladder in vitro.

Lower urinary tract symptoms are not only a serious health problem but also a substantial sociologic issue affecting human beings and companion animals. Estrogen deficiency is considered an etiologic factor of urinary incontinence in postmenopausal women and spayed female dogs. However, insufficient effectiveness of hormonal therapy has caused an intensive search for new therapeutic options. GnRH analogs have positive clinical effects in neutered female dogs suffering from incontinence, but the mechanism of action is not known. The aim of our study was to determine the effect of long-acting deslorelin acetate on the spontaneous activity of urinary bladder sections from a rabbit model of long-term estrogen deprivation. The study was conducted on 21 female New Zealand White rabbits divided into the following groups: control group, ovariohysterectomized (OHX) group, and ovariohysterectomized group given a deslorelin acetate implant. Urinary bladders were excised immediately after sacrifice, and the spontaneous activity of dorsal and ventral strips of the bladder body was examined in organ bath chambers. The amplitude and frequency of the spontaneous contractions were evaluated. Most of the sections developed spontaneous activity. Ovariohysterectomy caused a decrease in the amplitude of spontaneous contractions of the tissues obtained only from the dorsal part of the bladder body. After OHX, the frequency was higher compared with the control group in both parts of the bladder. Deslorelin acetate did not significantly affect the spontaneous contraction amplitude but caused a decrease in the frequency in the dorsal and ventral parts of the bladder. In conclusion, long-term changes in the levels of hormones and other regulatory substances associated with the reproductive system are related to altered spontaneous activity of the urinary bladder, which may impact the symptoms of urgency and incontinence appearing in women after menopause and in female animals after gonadectomy. However, long-acting deslorelin acetate partially reverses the effect of OHX on the spontaneous activity of the bladder. This process might underlie the positive effects of GnRH analogs in incontinent spayed female dogs.

Application of FTIR-ATR Spectroscopy to Determine the Extent of Lipid Peroxidation in Plasma during Haemodialysis.

During a haemodialysis (HD), because of the contact of blood with the surface of the dialyser, the immune system becomes activated and reactive oxygen species (ROS) are released into plasma. Particularly exposed to the ROS are lipids and proteins contained in plasma, which undergo peroxidation. The main breakdown product of oxidized lipids is the malondialdehyde (MDA). A common method for measuring the concentration of MDA is a thiobarbituric acid reactive substances (TBARS) method. Despite the formation of MDA in plasma during HD, its concentration decreases because it is removed from the blood in the dialyser. Therefore, this research proposes the Fourier Transform Infrared Attenuated Total Reflectance (FTIR-ATR) spectroscopy, which enables determination of primary peroxidation products. We examined the influence of the amount of hydrogen peroxide added to lipid suspension that was earlier extracted from plasma specimen on lipid peroxidation with use of TBARS and FTIR-ATR methods. Linear correlation between these methods was shown. The proposed method was effective during the evaluation of changes in the extent of lipid peroxidation in plasma during a haemodialysis in sheep. A measurement using the FTIR-ATR showed an increase in plasma lipid peroxidation after 15 and 240 minutes of treatment, while the TBARS concentration was respectively lower.

ß-adrenergic antagonists influence abdominal aorta contractility by mechanisms not involving ß-adrenergic receptors.

ß-adrenergic receptors (ß-AR) are widely distributed in the cardiovascular system, where they considerably contribute to the control of its functions. ß-blockers are commonly used in the treatment of disorders of the circulatory system. They act primarily by inhibiting cardiac ß-receptors. However, there are also reports of pleiotropic action of ß-blockers as well as of new compounds created to study ß3 adrenergic receptors. The study aimed to investigate additional mechanisms of action of ß-AR inhibitors in the rabbit abdominal aorta with emphasis on their action on α-adrenergic receptors and calcium influx. Responses to propranolol, betaxolol, metoprolol and SR59230A were evaluated in phenylephrine and PGF(2alpha) precontracted aortic rings. The effect of propranolol on the phenylephrine concentration-contraction curve was examined. Propranolol (≥ 10 µM) and SR59230A (≥ 0.1 µM) induced relaxations in phenylephrine-precontracted rings, while betaxolol and metoprolol had little effect. The ß-AR inhibitors produced further contraction of tissues preincubated with PGF(2alpha), excluding SR59230A, which after initial contraction, elicited marked relaxation at a concentration above 1 eM. 100 µM of propranolol caused a significant rightward shift of the concentration-contraction curve to phenylephrine with no reduction in the maximum response. Incubation of aortic rings in phentolamine reduced the maximal contraction to propranolol; verapamil pretreatment by contrast enhanced contractile response. In conclusion, SR59230A and propranolol most probably act as α1-AR competitive antagonists in the presence of phenylephrine in rabbit abdominal aortic rings. After α-ARs blockade, propranolol exerts a weak relaxing activity connected with Ca2+ channel inactivation. SR59230A at a high concentration acts on the rabbit aorta by an additional mechanism needing further investigation.

Nonspecific effects of ligands on the beta-adrenergic receptors in rabbit abdominal aorta in vitro.

The study was conducted on 30 New Zealand rabbits weighing 3-4 kg from which sample strips of the abdominal aorta were collected. The study investigated the in vitro reaction of rabbit aorta smooth muscle to ligands binding to beta-adrenergic receptors. The response of aortic strips to beta-adrenergic receptor agonists (dobutamine, isoproterenol, salbutamol) and the influence of beta-adrenergic receptor antagonists (propranolol, betaxolol) on contractile activity was determined. All tested agonists induced contraction of the rabbit abdominal aorta muscle in a concentration-dependent manner (dobutamine >> isoproterenol > salbutamol). Enhanced reaction to low concentrations of agonists (dobutamine, isoproterenol) after administration of propranolol and inhibition of contractility in the presence of high concentrations thereof (dobutamine, salbutamol) was observed. Maximal reaction to agonists decreased after betaxolol pretreatment. The results indicate that all the substances with beta-agonist activity also possess contracting properties (presumably by acting at alpha-adrenergic receptors), but are much weaker in the case of isoproterenol and salbutamol than for dobutamine. Propranolol and betaxolol reduce the contractile response of smooth muscle using probably other mechanisms than those associated with adrenergic receptors.