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1.
Low doses of endotoxin cause vasoconstriction and hypoperfusion of the digit, small intestine, and cecum in horses. To determine the potential cause of these vascular alterations, in vitro vascular responses of palmar digital arteries and veins were determined in 8 horses after intravenous (IV) infusion of 1 L 0.9% NaCl (control) and 0.1 μg/kg Escherichia coli 055:B5 endotoxin in 1 L of 0.9% NaCl (endotoxin-treated). Vessels were surgically removed under general anesthesia, cut into 4-mm vascular rings, suspended in tissue baths, and attached to force displacement transducers for measurement of vascular tension. Cumulative concentration response curves to acetylcholine, bradykinin, nitroprusside, norepinephrine, 5-hydroxytryptamine (serotonin), and endothelin were determined. Maximal relaxation or contraction and the concentrations needed to produce 50% maximal relaxation or contraction were determined. Palmar digital arteries from endotoxin-treated horses relaxed significantly less in response to acetylcholine and bradykinin (endothelium-dependent), but not to nitroprusside (endothelium-independent) when compared with arteries from control horses. Digital arteries from endotoxin-treated horses also contracted significantly more with norepinephrine but less with serotonin. Digital veins responded less than digital arteries. In another study, vascular reactivity experiments documented that acetylcholine and bradykinin were endothelium-dependent vasodilators (endothelium-denuded vessels relaxed less than control vessels) in palmar digital vessels. Additionally, maximal relaxations for both vasodilators were significantly inhibited by N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist, suggesting that acetylcholine and bradykinin cause relaxation through the nitric oxide pathway. The data from these studies indicate that low dose endotoxin impairs endothelium-dependent relaxation and augments adrenergic contraction of palmar digital arteries in horses.  相似文献   

2.
Endotoxaemia is a syndrome linked to the development of equine laminitis; however, the relationship between them is uncertain. The aim of this experiment was to evaluate the effect of an experimental acute sublethal endotoxaemia model on in vitro equine palmar digital vascular reactivity. Rings of arteries and veins of each forelimb were obtained from 11 clinically healthy horses submitted to two surgical procedures, 3 weeks apart. Before the second surgery, 0.25 microg/kg of lipopolysaccharide from Escherichia coli O55:B5 in saline, was administered i.v. in 30 min. After 3 h, the vessels were harvested and submitted to in vitro vascular reactivity experiments and histopathology. The response to depolarizing Krebs solution (DKS, 40 mm), phenylephrine (PHE), acetylcholine (ACh) and sodium nitroprusside (SNP) were evaluated. All horses showed colic pain and watery diarrhoea, tachycardia, tachypnea, hyperthermia and leucopenia. Concentration-response curve (CRC) to PHE was shifted to the left in arteries rings from endotoxemic horses without any effect on vein rings. The CRC to ACh was shifted to the right with a reduction in the maximal response. The response to SNP and DKS was similar between groups. There was no evidence of histopathological effects. The increased response to PHE in digital arteries together with a reduction of the endothelium-dependent response to ACh in arteries and veins, confirm the existing reports where endotoxaemia was found to modify the digital vascular reactivity during the acute phase. As the digital endothelial function is impaired, there may be an increased potential to develop a digital prothrombotic state with a reduced vasodilatory capacity.  相似文献   

3.
The in vitro reactivity of vasoconstrictive mediators that are implicated in acute laminitis was determined in palmar and plantar digital arteries and veins obtained from healthy horses and in palmar digital vessels of horses with early laminitis (Obel grade I). To obtain baseline reactivity data, 3 experiments were conducted, using healthy horses: (1) the reactivity of palmar and plantar digital arteries and veins to angiotensin II, norepinephrine, and 5-hydroxytryptamine (serotonin) were compared; (2) the direct effects of bacterial endotoxin on vascular reactivity were assessed; and (3) the reactivity of palmar digital arteries and veins to angiotensin II, norepinephrine, prostaglandin F2 alpha (PGF2 alpha), serotonin, and a thromboxane-endoperoxide analog (U46619) were determined. The vascular reactivity of these same 5 vasoconstrictors then was determined in horses with early laminitis and was compared with data from healthy (control) horses. Obel grade-I laminitis was experimentally induced in horses, using carbohydrate overload. Dose responses were conducted for each agent at concentrations between 10(-8)M and 10(-4)M. The potency of a drug was defined as the mean effective concentration necessary to induce 50% of maximal contraction (EC50). There were no differences in EC50 concentrations and in maximal contractions between forelimb and hind limb arteries and veins for angiotensin II, norepinephrine, and serotonin. Incubation with endotoxin had no effect on the reactivity of arteries and veins to angiotensin II, norepinephrine, and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

4.
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5.
Reasons for performing study: One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Hypothesis and objectives: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at 37°C, 2 g tension was applied and the rings allowed to equilibrate for 45 min. Of the 4 rings of each vessel type, one was used as a control. One each of the remaining 3 rings was used for incubation with insulin (to induce resistance), wortmannin (to block PI3‐kinase) and PD‐098059 (to block MAP‐kinase), respectively, for 30 min. After the incubation period, the rings were contracted with phenylephrine. When the response reached a plateau, a single dose of insulin was added to the baths and the response of each ring monitored for 30 min. Results: Insulin relaxed the control rings and those treated with PD 098059 but contracted those pretreated with insulin and wortmannin. Normal relaxation responses of the rings were converted to contractions by insulin resistance. Insulin resistance was confirmed by the qualitative response of insulin‐incubated and wortmannin‐incubated rings. Conclusions: This study demonstrated successful induction of insulin resistance in both arterial and venous rings. It also suggested that the MAP‐kinase pathway plays a minor role in controlling vasomotor tone under normal physiological conditions. Potential relevance: The study suggests that the induction of insulin resistance in equine palmar digital vessel rings is reliable and provides a good in vitro model for studying the vascular insulin resistance which may occur in equine laminitis.  相似文献   

6.
OBJECTIVE: To measure and compare palmar digital venous plasma nitric oxide (NO) concentrations and digital arterial blood flow after application of topical nitroglycerine (NTG). STUDY DESIGN: Experimental study. ANIMALS: Healthy adult horses (n=8). METHODS: Digital blood flow was measured by an ultrasonic Doppler flow probe surgically implanted around the medial palmar digital artery. Blood was collected from a catheter placed in the medial palmar digital vein for quantification of NO. NTG patches, NTG ointment or control patches were placed over the palmar digital vessels at the level of the fetlock. Two horses had an intra-arterial infusion of an NTG solution into the medial palmar digital artery in a pilot study. RESULTS: Digital arterial blood flow did not change significantly with application of the NTG patches, NTG ointment, or control patches. There were no statistically significant or biologically important changes in digital venous NO concentrations across time or between treated and control horses. In the pilot study, digital arterial blood flow and palmar digital venous NO concentrations increased with intra-arterial infusion of NTG. CONCLUSIONS: In clinically healthy horses, digital arterial blood flow and digital venous plasma NO concentrations did not change significantly with application of the NTG patches/ointment. These treatments are unlikely to have an effect on the digital vasculature of laminitic horses, however, further investigation is warranted. CLINICAL RELEVANCE: Although NTG patches have been used as a method of decreasing vasomotor tone and improving digital blood flow in horses with laminitis, this study provides evidence in healthy conscious horses that this treatment is not effective in altering digital blood flow.  相似文献   

7.
In coronary arterial rings isolated from horses, 10--8-10-6 mol/l acetylcholine (ACh) induced concentration-dependent contractions which were potentiated by the removal of endothelium and by pretreatment with I,-nitro-arginine (LNAG) or methylene blue (MB). Relatively lower concentrations of Ach 10-14-10-8 mol/l) induced relaxation when the coronary rings were contracted by phenylephrine (PE). ACh-induced contractions in the coronary rings without endothelium were competitively inhibited by each muscarinic subtype selective antagonist in the following order of potency: 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) > pirenzepine ≥ parafluoro-hexahydrosiladiphenidol (pFHHSiD) > methoctramine. ACh-induced relaxation in the rings with endothelium was inhibited by LNAG or MB, and by each selective antagonist in the following order of potency: 4-DAMP < pFHHSiD ≥ pirenzepine ≥ methoctramine. These results suggest that the ACh-induced contraction and relaxation in equine coronary arteries are mediated mainly by an M3-receptor located on the smooth muscle cells and endothelial cells, respectively, and that the stimulation of the M3-receptor on the endothelial cells liberates nitric oxide.  相似文献   

8.
OBJECTIVE: To describe submural histopathologic changes attributable to peracute laminitis in horses. ANIMALS: 20 adult horses. PROCEDURE: A concurrent-control design was used to compare laminar lesions in 10 horses subjected to carbohydrate-induced laminitis with laminar characteristics of 10 sex- and aged-matched control horses with normal feet. Horses in the treatment group were administered an overload of carbohydrate. Tissues were obtained by biopsy 4 to 8 hours after onset of lameness or 72 hours after administration of the carbohydrate overload when lameness did not develop. Sections were stained with H&E, Masson's trichrome, and periodic acid-Schiff stains. Histopathologic changes were analyzed to detect differences between groups and to correlate epidermal changes with severity and duration of lameness. RESULTS: Analysis indicated that dermal and epidermal lesions were evident despite lack of visible separation of the epidermal basement membrane, can be found in horses without detectable lameness, and were nonspecific and progressive following onset of lameness. Furthermore, severity and location of lesions were associated with severity and duration of lameness. CONCLUSION AND CLINICAL RELEVANCE: These observations are consistent with the concept that separation of the laminar epithelial basement membrane is a delayed step in the pathogenesis of acute laminitis, digital vascular hypoperfusion is an underlying cause for laminitis, and the potential for repeated episodes of subclinical laminitis may underlie the development of structural and mechanical changes consistent with chronic laminitis despite lack of clinical signs of acute laminitis.  相似文献   

9.
OBJECTIVE: To evaluate changes in digital vascular function in horses with carbohydrate overload (CHO)-induced laminitis and determine the effects of an endothelin (ET) receptor antagonist and nitroglycerin on laminitis-associated vascular dysfunction. ANIMALS: 20 adult horses without abnormalities of the digit. PROCEDURES: Hemodynamic variables were recorded before (baseline) and hourly after all horses were administered a CHO ration via nasogastric tube. In 4 groups of 5 horses each, saline (0.9% NaCl) solution or ET receptor antagonist (10(5)M in digital blood) was administered into the digital arterial circulation according to 1 of 2 schedules. During anesthesia, blood flow; arterial, venous, and capillary pressures; and total, precapillary, and postcapillary resistances were measured in an isolated perfused digit of each horse. In all groups, nitroglycerin was infused (10(5)M in digital blood), and digital microvascular assessments were repeated. RESULTS: The CHO caused a significant decrease in right atrial pressure by 14 hours that was not affected by administration of saline solution or ET receptor antagonist. In isolated digits of anesthetized horses, CHO resulted in a significant decrease in digital blood flow associated with a significant increase in total and postcapillary resistances. Treatment with the ET receptor antagonist and nitroglycerin caused a significant decrease in total resistance. Postcapillary resistance was significantly decreased following treatment with the ET receptor antagonist but was not altered by treatment with nitroglycerin. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with an ET receptor antagonist and nitroglycerin resulted in significant improvement in vascular resistance in isolated perfused digits of anesthetized horses with CHO-induced laminitis.  相似文献   

10.
OBJECTIVE: To determine whether a unique dihydropyridine (BAYTG 1000) would be beneficial in preventing laminitis in horses. ANIMALS: 16 clinically normal adult horses. PROCEDURE: 8 pairs of horses were used in a controlled double-blind study, using sex- and age-matched horses randomly assigned to treatment or control groups. Horses were subjected to carbohydrate overload to induce laminitis. Treated horses were administered BAY TG 1000 (30 mg/kg, PO, q 24 h) for 3 days. Hoof wall surface temperature (HWST) and lameness were recorded at 4-hour intervals. The HWST was adjusted on the basis of time of onset of lameness and evaluated, using a repeated-measures ANOVA. Lameness 8 hours after onset and clinical status 72 hours after onset of lameness were evaluated, using Mann-Whitney procedures. RESULTS: Analysis revealed that BAYTG 1000 did not decrease the incidence of lameness but significantly ameliorated prodromal hypothermia, lessened the severity of lameness 8 hours after onset of lameness, and improved the clinical status of horses 72 hours after onset of lameness. CONCLUSION AND CLINICAL RELEVANCE: Results support the conclusion that BAYTG 1000 was protective when used in prevention of laminitis. The drug decreased severity and improved clinical status (recovery) of induced lameness, which was interpreted to mean that the drug's actions were on mechanisms important but secondary to primary causal mechanisms of laminitis. Therefore, drugs that enhance digital perfusion via alteration of rheologic activity may have potential use in the prevention and management of laminitis in horses.  相似文献   

11.
OBJECTIVE: To evaluate the use of hoof wall surface temperature (HWST) as an indirect indicator of digital perfusion and to describe HWST patterns during the prodromal and acute phases of carbohydrate-induced laminitis in horses. ANIMALS: 30 adult horses without foot abnormalities. PROCEDURES: Three experiments were performed. In the first, HWST was measured in 2 groups of horses acclimatized to hot (n = 6), or cold (6) environments and exposed to cold (15 C) ambient temperature. In the second experiment, HWST were measured in both forefeet of 6 horses before and after application of a tourniquet to 1 forefoot to induce vascular occlusion. In the third experiment, HWST were recorded in 12 horses before and during the prodromal and acute phases of carbohydrate-induced laminitis. RESULTS: Mean HWST of hot-acclimatized cold-challenged horses was significantly less than that of cold-acclimatized cold-challenged horses at all times. Transient episodes of high HWST were observed during prolonged cold-induced vasoconstriction. Hoof wall surface temperature significantly decreased during arterial occlusion and increased during reperfusion. Digital hypothermia was observed during the prodromal phase of carbohydrate-induced laminitis. CONCLUSIONS AND CLINICAL RELEVANCE: Determination of HWST is a valid technique to evaluate digital perfusion under appropriate controlled conditions in horses. Digital hypothermia detected during the prodromal phase of laminitis is consistent with decreased digital vascular perfusion or metabolic activity. If administered to horses during the prodromal phase, agents that enhance digital perfusion may prevent development of laminitis.  相似文献   

12.
The effects of endotoxin on β-adrenergic-mediated relaxation were investigated in the equine digital artery (EDA). Possible involvement of cyclooxygenase-2 (COX-2) in endotoxin-induced effects and basal EDA β-adrenoceptor functionality was also evaluated. Endothelium-intact (e(+)) and/or -denuded (e(-)) EDA rings were incubated overnight with lipopolysaccharide (LPS), LPS+NS398 (selective COX-2 inhibitor) or NS398 alone. Vessel rings were then mounted in organ baths and relaxant responses to isoproterenol (ISOP) recorded on U44069-induced pre-contraction. Response to ISOP was further evaluated in either incubated or freshly isolated (e(-)) rings acutely exposed to NS398. Fresh and incubated (e(-)) EDAs were also analysed for COX-2 expression by Western blotting. LPS caused endothelium-dependent enhancement of β-adrenergic mediated relaxation. NS398 did not reverse endotoxin effects, suggesting that COX-2 did not have a mediating role. In the absence of LPS, NS398 significantly increased ISOP-induced relaxation. This finding, together with immunoblot detection of COX-2 in both fresh and incubated (e(-)) vessels, revealed the existence of a constitutive COX-2 exerting tonic inhibitory modulation on EDA β-adrenergic-mediated relaxation. The results support the possible role of endotoxin in the vascular disturbances associated with equine laminitis. Moreover, the involvement of COX-2 in the physiological regulation of EDA tone warrants further clinical investigation into the efficacy and safety of selective COX-2 inhibitors on digital circulation in horses.  相似文献   

13.
To investigate the vascular smooth muscle dysfunction of septic shock, in vitro isometric responses to phenylephrine (PE) and acetylcholine (ACh) were evaluated in aortic rings, with and without endothelium (± E), removed from male Wistar rats 1.5, 3 and 6 h after intravenous (i.v.) administration of 5 mg/kg lipopolysaccharide (LPS) or vehicle. A reduction in maximum contraction (±E) and sensitivity (-E) to PE were identified at 6 but not at 1.5 or 3 h. Maximum relaxation to ACh (+ E) was not affected by LPS treatment but sensitivity was increased at 1.5 and 3 h. Having identified 6 h as the time at which the most pronounced changes were observed, further studies at this interval found that maximum contraction to potassium chloride (±E), prostaglandin F2a (+ E) and detomidine (-E) and relaxation to salbutamol (-E) were less in aortic rings from endotoxaemic rats. Sensitivity to KCl (±E), PGF2a (- E) and detomidine (- E) was also reduced. Relaxation to sodium nitroprusside and atrial natriuretic peptide was not changed. These results suggest that attenuated pressor responses to a variety of vasoactive agents may be expected in patients 6 h after systemic exposure to endotoxin and that this vasoplegia may influence the vascular side-effects of therapeutic agents.  相似文献   

14.
Reasons for performing study: Hyperinsulinaemia is known to induce laminitis experimentally in healthy ponies with no history of the condition. Horses are more insulin sensitive than ponies and whether prolonged hyperinsulinaemia and euglycaemia would have a similar laminitogenic effect requires study. Objectives: To determine if laminitis results when the prolonged euglycaemic hyperinsulinaemic clamp technique (p‐EHC) is applied to clinically normal Standardbred horses, and to monitor hoof wall temperature seeking an association between vascular activity and laminitis development. Methods: Eight young, clinically normal Standardbred horses were assigned into 4 pairs and within each pair, one was assigned randomly to either treatment (n = 4) or control (n = 4) groups. Treated horses received continuous infusions of insulin and glucose until clinical signs of laminitis developed, at which point the horses were subjected to euthanasia. Control horses received an equivalent volume of a balanced electrolyte infusion for the same period. Hoof wall surface temperature (HWST) was monitored continuously throughout the experimental period. Results: All horses in the treatment group were calculated to have normal insulin sensitivity. All treated horses, and none in the control group, developed laminitis (P = 0.01). Pronounced digital pulses were a feature of the treatment group, while insignificant digital pulses occurred in control horses. HWST was higher and less variable in treated horses once hyperinsulinaemia was established. Conclusions: Healthy Standardbred horses subjected to prolonged hyperinsulinaemia develop laminitis within 48 h, demonstrating that laminitis in horses can be triggered by insulin. Potential relevance: Insulin resistance and the associated hyperinsulinaemia place horses and ponies at risk of developing laminitis. This study demonstrates a need for prompt management of the persistent hyperinsulinaemia seen in some endocrinopathies.  相似文献   

15.
OBJECTIVE: To determine and compare the number, type, location, and distribution of apoptotic epidermal cells in the laminae of clinically normal horses and horses with laminitis. SAMPLE POPULATION: Formalin-fixed samples of digital lamellar tissue from 47 horses (including clinically normal horses [controls; n = 7], horses with acute [4] and chronic [7] naturally acquired laminitis, and horses with black walnut extract-induced [11] or carbohydrate overload-induced [18] laminitis). PROCEDURE: Blocks of paraffin-embedded lamellar tissues were stained for DNA fragmentation with the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) technique. Differential immunohistochemical staining for caspases 3 and 14 were used to confirm apoptosis. RESULTS: The number of TUNEL-positive epidermal cells per 0.1 mm of primary laminae was significantly greater in the acute laminitis group than in the other groups. In the acute laminitis group, there were 17 and 1,025 times as many TUNEL-positive basal layer cells and keratinocytes, respectively, compared with the control group. Apoptosis of TUNEL-positive basal layer cells was confirmed by results of caspase 3 immunohistochemical staining. The TUNEL-positive keratinocytes did not stain for caspases 3 or 14. CONCLUSIONS AND CLINICAL RELEVANCE: The large number of apoptotic basal layer cells detected in the lamellar tissue of horses with acute naturally acquired laminitis suggests that apoptosis may be important in the development of acute laminitis. The role of the large number of TUNEL-positive keratinocytes detected in the interface of primary and secondary epidermal laminae of horses with acute laminitis remains to be elucidated.  相似文献   

16.
REASONS FOR PERFORMING STUDY: Equine laminitis purportedly involves haemodynamic dysfunction at the level of the laminar vasculature. However, to date, no studies have been performed characterising the function of laminar arteries and veins during the prodromal stages of equine laminitis. HYPOTHESIS: That the prodromal stages of laminitis are associated with contractile dysfunction of the equine laminar vasculature. OBJECTIVE: To assess contractile function of laminar arteries and veins to phenylephrine (PE) and 5-hydroxytryptamine (5-HT). METHODS: Horses were administered black walnut heartwood extract (BWHE) or water (control horses) via nasogastric intubation. After euthanasia, laminar vessels (100-800 microm internal diameter) were isolated and mounted on small vessel myographs to assess contractile function. RESULTS: Contractile responses to PE or 5-HT were identical in laminar arteries isolated from either control horses or those administered BWHE. In contrast, responses to PE or 5-HT were significantly reduced in laminar veins isolated from BWHE-administered horses when compared with laminar veins isolated from control horses. CONCLUSIONS AND POTENTIAL RELEVANCE: These results are consistent with the prodromal stages of laminitis being associated with selective dysfunction of laminar veins. Further studies are required to discern the precise nature of this dysfunction and its potential relevance to the pathogenesis of acute laminitis in the horse and possible therapeutic targets for treatment.  相似文献   

17.
Haemoglobin-based oxygen carriers have been developed as 'blood substitutes'. Early cross-linked haemoglobins caused marked vasoconstriction, however, polymerized haemoglobin solutions, such as the bovine product haemoglobin glutamer-200 (bovine) (Hb-200), are said to have lesser vascular effects. The aim of this study was to quantify the effect of Hb-200 on isolated rat arterial rings. The actions of Hb-200 were investigated using rings of aorta and second-order mesenteric arteries from female Wistar rats. The arterial rings were mounted for isometric tension recording. Addition of Hb-200 (1 microM) to arterial rings, precontracted with phenylephrine (50-70% maximum phenylephrine-induced tone), resulted in vasoconstriction. Addition of Hb-200 to arteries precontracted with phenylephrine and relaxed with acetylcholine (1 microM) also caused contraction. Furthermore preincubation with Hb-200 (1 microM) enhanced the response to phenylephrine (1 nm to 10 microM) and impaired acetylcholine-induced relaxation (10 nm to 10 microM). Responses to Hb-200 were similar to those in response to the nitric oxide (NO) synthase inhibitor, NG-nitro-l-arginine methyl ester (L-NAME, 100 microM), alone or in combination with Hb-200. These data demonstrate that Hb-200 has a significant vasoconstrictor effect similar to L-NAME. Thus the vascular actions of Hb-200 are consistent with activity as a NO scavenger. This may have implications for the clinical use of Hb-200.  相似文献   

18.
We have previously shown that interleukin-1 beta relaxes vascular smooth muscle by the NO-dependent and independent mechanisms (Takizawa et al.: Eur. J. Pharmacol. 330: 143-150, 1997). In this study, we investigated the mechanism of NO-independent relaxation. Treatment of the rat aorta with interleukin-1 beta for 24 hr inhibited the high-K+ induced contraction by decreasing cytosolic Ca2+ level ([Ca2+]i). The relationship between [Ca2+]i and tension in intact muscle and the pCa-tension curves in permeabilized muscle suggested that Ca2+ sensitivity of contractile element was not changed after the interleukin-1 beta-treatment. After a treatment with interleukin-1 beta for 24 hr, contractile effects of phenylephrine (1 microM-10 microM) were markedly inhibited in the presence of L-NMMA (100 microM) applied to inhibit NO synthesis. A blocker of ATP-sensitive K+ channel, glibenclamide (1 microM), partially recovered the interleukin-1 beta-induced inhibition. In contrast, a blocker of Ca(2+)-activated K+ channel, charybdotoxin (0.1 microM), was ineffective. These results suggest that membrane hyperpolarization due to activation of ATP-sensitive K+ channels may partly be responsible for the NO-independent mechanism of interleukin-1 beta-induced inhibition of vascular smooth muscle contraction.  相似文献   

19.
OBJECTIVE: To study expression of interleukin-1beta (IL-1beta) in the digital laminae of horses in the prodromal stage of experimentally induced laminitis. ANIMALS: 8 healthy adult horses with no signs of laminitis. PROCEDURES: Black walnut extract was administered via nasogastric tube to 4 horses, and water was administered to the remaining 4 (controls). Complete blood counts and physical examinations were performed every 30 minutes after administration of black walnut extract or water. General anesthesia was induced when total WBC count decreased by 30% in horses given the black walnut extract and 3 hours after water administration in control horses. The left forefoot was perfusion fixed with neutral-buffered 10% formalin, and paraffin-embedded sections of the digit were used for in situ hybridization with an equine-specific IL-1beta probe. RESULTS: IL-1beta mRNA expression was observed in perivascular cells of the small laminar venules and capillaries in all 4 horses given black walnut extract and in interstitial cells remote from the microvasculature in 1 of the 4. Other cellular components of the laminar tissue and cellular components of the digital arterioles and veins did not exhibit IL-1beta mRNA expression. Expression of IL-1beta mRNA was not detected in laminae from control horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IL-1beta mRNA is expressed by perivascular cells in the laminar tissues of horses in the prodromal stage of experimentally induced laminitis. This provides evidence of an inflammatory process during the prodromal stage of laminitis, indicating that local digital proinflammatory cytokine expression may be an initiating factor in laminitis.  相似文献   

20.
OBJECTIVE: To determine in vitro vasoactive potency of monoamines formed in the cecum and found in the systemic circulation of horses. SAMPLE POPULATION: Segments of digital blood vessels obtained from 6 healthy mixed-breed horses and ponies euthanatized at an abattoir and platelets isolated from 4 healthy ponies. PROCEDURE: Paired rings of digital artery and vein from the same horse were examined, and isometric tension was recorded. Concentration-response curves for tryptamine (TRP), tyramine (TYR), phenylethylamine (PEA), isoamylamine (IAA), and isobutylamine (IBA) were obtained. Vasoconstrictor mechanisms were investigated for TRP and TYR by the use of antagonists. Washed platelets loaded with [3H]-5-hydroxytryptamine (5-HT) were incubated with monoamines; the amount of radioactivity displaced after 30 minutes was estimated. RESULTS: TRP, TYR, and PEA were potent constrictors of arteries and veins, with TRP and TYR being more potent in veins than arteries. Constrictions induced by TYR were inhibited by benextramine (alpha-antagonist) and nisoxetine (neuronal-uptake blocker), whereas TRP responses were inhibited by ketanserin (5-HT receptor antagonist). All 5 amines displaced 5-HT from platelets with the order of potency being TYR > TRP > PEA > IAA > IBA. CONCLUSIONS AND CLINICAL RELEVANCE: Amines from the equine cecum cause digital vasoconstriction. The most potent (TRP and TYR) cause selective venoconstriction. Tyrosine activates predominantly alpha-adrenoceptors through the release of neuronal norepinephrine, whereas TRP activates 5-HT receptors. All amines tested released 5-HT from platelets. Amines formed in the cecum and released into the systemic circulation warrant additional investigation as trigger factors for digital ischemia and subsequent laminitis.  相似文献   

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