Effects of a peripheral alpha2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs

OBJECTIVE: To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS: After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.     

Effects of a specific thromboxane synthetase inhibitor on thromboxane generation and excretion in healthy dogs

A specific thromboxane synthetase inhibitor, 3-methyl-2 (3-pyridyl)-1-indoleoctanoic acid (CGS 12970) was administered orally to 6 healthy adult Beagles at a dosage of 30 mg/kg of body weight. Blood generation of thromboxane B2 and urinary excretion of thromboxane B2 were measured before and after administration of CGS 12970. Although 97 +/- 0.4% inhibition of thromboxane B2 generation was observed within 2 hours after a single dose of CGS 12970 was administered orally, an effect on urinary excretion of thromboxane B2 was not observed. Additionally, oral administration of 30 mg/kg every 12 hours resulted in 80 +/- 14% inhibition of thromboxane B2 generation but had no effect on urinary thromboxane B2 excretion.     

Endotoxin-induced digital vasoconstriction in horses: associated changes in plasma concentrations of vasoconstrictor mediators

REASONS FOR PERFORMING STUDY: Lipopolysaccharide (LPS) infusion reduces digital perfusion, but the mediators responsible remain undetermined. OBJECTIVES: To identify vasoconstrictor mediators released following LPS infusion and relate their appearance in plasma to digital blood flow alterations. METHODS: Blood flow in the lateral digital vessels of 6 Thoroughbred horses, following a 30 min infusion of LPS (E. coli 055:B5; 30 ng/kg), was measured using Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures (HWST and CBST) were made. Serial blood samples were collected and plasma LPS, tumour necrosis factor alpha (TNFalpha), 5-HT, thromboxane B2 (TxB2) and endothelin measured. RESULTS: Plasma LPS concentrations reached a maximum of 13.2 pg/ml during the infusion, followed by an increase in plasma TNFalpha concentration. Digital arterial and venous blood flow decreased by 43 and 63%, respectively; HWST and CBST similarly decreased. Systemic blood pressure remained unaltered. Plasma concentrations of TxB2 and 5-HT increased, coinciding with the onset of digital hypoperfusion. Plasma endothelin concentrations remained unchanged. CONCLUSIONS: The temporal relationship between the onset of digital hypoperfusion and increases in plasma 5-HT and TxB2 concentrations is consistent with these platelet-derived mediators being associated with LPS-induced laminitis. POTENTIAL RELEVANCE: These experimental data support the use of anti-platelet therapy in the prevention of laminitis associated with endotoxaemic conditions.     

Cardiovascular changes after bone marrow transplantation in dogs with mucopolysaccharidosis I

Five dogs with mucopolysaccharidosis I, 3 of which had been treated with bone marrow transplantation (BMT), were evaluated for 20 months with electrocardiography, thoracic radiography, and M-mode and 2-dimensional echocardiography. Treated and untreated (control) dogs had widened P waves on ECG. Thoracic radiographs remained normal for all dogs throughout the study. Thickening of the mitral valve was observed on echocardiograms of dogs in both groups, but the untreated dogs appeared to have thicker valves. Concentrations of glycosaminoglycans in the mitral valves and myocardium were higher in control dogs than in treated dogs. Markedly large aortic root diameters were observed on echocardiograms in both untreated dogs, but aortic root diameters remained normal in treated dogs. Echocardiography, but not electrocardiography, was useful in monitoring heart enlargement in each dog. Dogs treated with BMT generally had less severe cardiac changes and slower disease progression than control dogs.     

Endotoxin-induced hematologic and blood chemical changes in ponies: effects of flunixin meglumine, dexamethasone, and prednisolone

To evaluate the effect of certain drugs on hematologic changes, blood chemical values, and survival in endotoxin shock, anesthetized ponies were given (IV) endotoxin (Escherichia coli O55:B5) and then treated as follows: Group A ponies--given a saline infusion at 5 minutes and at 3 hours after they were given endotoxin; group B ponies--given flunixin meglumine at 5 minutes and at 3, 6, 9, and 24 hours after they were given endotoxin; group C ponies--treated with dexamethasone; and group D ponies--treated with prednisolone at 5 minutes and at 3, 9, and 24 hours after they were given endotoxin. Anesthesia was maintained for 4 hours, after which time the ponies were allowed to recover. Throughout the experiment, samples of blood were collected for blood gas, hematologic, and blood chemical values. The endotoxin effects were seen in the 4 groups: lactic acidosis, prolonged coagulation times, leukopenia, hemoconcentration, and elevated blood chemical values. Although none of the treatments prevented the effects of endotoxin, changes were less severe and survival times were longer in ponies treated with flunixin meglumine.     

Ultrasonographic assessment of hemodynamic changes in the portal vein during surgical attenuation of congenital extrahepatic portosystemic shunts in dogs

OBJECTIVE: To determine portal hemodynamic changes associated with surgical shunt ligation and establish ultrasonographic criteria for determining the optimal degree of shunt narrowing and predicting outcome. DESIGN: Case series. ANIMALS: 17 dogs, each with a single congenital extrahepatic portosystemic shunt. PROCEDURE: Pre- and postligation flow velocities and flow directions were determined by Doppler ultrasonography intraoperatively in the shunt and in the portal vein cranial and caudal to the shunt origin. Outcome was evaluated 1 month after surgery by measuring blood ammonia concentration and performing abdominal ultrasonography. RESULTS: Hepatofugal flow was detected in 9 of 17 dogs before shunt attenuation in the portal segment that was between the shunt origin and the entering point of the gastroduodenal vein. If hepatofugal flow became hepatopetal after shunt ligation, hyperammonemia resolved. Hepatofugal portal flow was caused by blood that flowed from the gastroduodenal vein toward the shunt. Shunt attenuation converted hepatofugal flow to hepatopetal in the shunt in 12 of 17 dogs. Chronic portal hypertension developed or perioperative death occurred when the portal congestion index caudal to the shunt origin increased by > 3.6 times. CONCLUSIONS AND CLINICAL RELEVANCE: After hepatopetal flow in the cranial portal vein and the shunt is established, further shunt narrowing is contraindicated. Increase of the portal congestion index caudal to the shunt > 3.5 times should be avoided. Poor outcome because of severe hypoplasia of the portal branches can be expected if the flow direction remains hepatofugal after shunt occlusion cranial to the shunt origin.     

The hemodynamic effects of intrathecal oxytocin in normal dogs

OBJECTIVE: To evaluate the hemodynamic effects produced by intrathecal administration of oxytocin in healthy isoflurane-anesthetized dogs. STUDY DESIGN: Prospective single-dose trial. ANIMAL POPULATION: Six healthy purpose-bred adult dogs weighing between 7.3 and 14.5 kg. METHODS: Dogs were anesthetized with isoflurane and instrumented. Oxytocin at a dosage of 1.6 microg/kg was administered intrathecally at the cisternal space at time 0. Hemodynamic data were recorded immediately before and at 1, 5, 15, 30, and 60 minutes after oxytocin administration. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. A P < .05 was considered significant. RESULTS: Baseline values +/- standard error of the mean for heart rate, mean arterial pressure, central venous pressure, cardiac output, systemic vascular resistance, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, and pulmonary vascular resistance were 101 +/- 11 beats/minute, 76 +/- 7 mm Hg, 4 +/- 4 mm Hg, 1.9 +/- 0.7 L/min, 3834 +/- 2556 dynes x sec/cm5, 14 +/- 3 mm Hg, 4 +/- 2 mm Hg, and 430 +/- 201 dynes x sec/cm5, respectively. Variations from the baseline values were seen in all parameters after intrathecal oxytocin administration, but no statistically significant differences were found. CONCLUSION: The intrathecal injection of 1.6 microg/kg of oxytocin is associated with minimal hemodynamic effects during isoflurane anesthesia. CLINICAL RELEVANCE: This study revealed no clinically significant deleterious effects from the intrathecal administration of oxytocin, and investigations into its use as a perioperative analgesic are therefore warranted.     

Role of ovarian progesterone and potential role of prostaglandin F2alpha and prostaglandin E2 in modulating the uterine response to infectious bacteria in postpartum ewes

In sheep and cattle, the postpartum uterus is resistant to bacterial challenge until after corpora lutea develop. A 2 x 2 factorial arrangement of treatments was used to determine whether prostaglandins may mediate the effects of progesterone in transforming the postpartum uterus from resistant to susceptible. On d 14 postpartum, ewes (n = 6/group) were ovariectomized or sham ovariectomized, and the vena cava was catheterized for daily collection of uteroovarian-enriched blood. From d 15 to 20, ewes received twice daily intramuscular injections of progesterone in sesame oil or plain sesame oil. On d 20, each uterus received 75 x 10(7) cfu of Arcanobacterium pyogenes and 35 x 10(7) cfu of Escherichia coli. Uteri were collected on d 25 and examined for signs of infection. For each blood sample, unstimulated and mitogen-stimulated lymphocyte proliferation was measured as [3H]thymidine incorporation, smears were prepared for differential white blood cell (WBC) counts, and progesterone, prostaglandin F2alpha, (PGF2alpha), and prostaglandin E2 (PGE2) were quantified. All 12 progesterone-treated, but only two of the 12 oil-treated, ewes developed uterine infections (P < 0.001). Progesterone treatment increased (P < 0.001; 3.1 vs 1.5 ng/mL) and ovariectomy decreased (P < 0.001; 3.7 vs 0.9 ng/mL) vena caval progesterone. Progesterone treatment reduced (P < 0.01) PGF2alpha, (303.9 vs 801.3 pg/mL), and PGF2alpha was greater (P < 0.05) before than after inoculation (626.4 vs 478.8 pg/mL). The PGE2 concentration was greater in progesterone-treated, ovary-intact ewes than in ewes in the other groups (ovariectomy x progesterone treatment; P < 0.01). Ovariectomy increased (P < 0.005; 4.4 vs 2.9 pmol) and progesterone treatment decreased (P < 0.05; 3.2 vs 4.1 pmol) concanavalin A-stimulated lymphocyte proliferation. Ovariectomy increased lipopolysaccharides-stimulated proliferation (P < 0.05; 2.4 vs 1.9 pmol). For neutrophils per 100 WBC, the ovariectomy x progesterone and progesterone x period interactions were significant (P < 0.01). The ovariectomy x progesterone interaction was significant (P < 0.01) for lymphocytes per 100 WBC. Ovariectomy decreased monocytes (P < 0.001; 10 vs 13) and increased eosinophils (P < 0.001; 10 vs 5) per 100 WBC. Progesterone makes the postpartum uterus in ewes susceptible to infection, but ovariectomy allows ewes to remain resistant; uterine prostaglandins may mediate this change. This model creates opportunities to determine the mechanisms responsible for the shift from resistance to susceptible.     

Acute hemodynamic effects of hydralazine in dogs with chronic mitral regurgitation

The hemodynamic response to hydralazine administration was evaluated in 6 conscious small dogs with chronic mitral regurgitation. All dogs underwent invasive and noninvasive hemodynamic monitoring before and after hydralazine administration. Cardiac output and pulmonary capillary wedge pressure were measured with a Swan-Ganz thermodilution catheter. Systemic arterial blood pressure (AP) was measured directly by inserting a needle into the femoral artery. Standard M-mode echocardiograms and thoracic radiographs were obtained. Other hemodynamic variables were calculated. Base-line hemodynamic variables were altered severely in all dogs. Hydralazine decreased mean arterial blood pressure from 104 +/- 18 (mean +/- SD) to 78 +/- 12 mm of Hg (P less than 0.005), total systemic resistance index from 2,946 +/- 625 to 1,261 +/- 420 dynes-s-cm-5m2 (P less than 0.005), and pulmonary capillary wedge pressure from 40 +/- 5 to 26 +/- 3 mm of Hg, (P less than 0.005). Cardiac index increased from 2.92 +/- 0.72 to 5.36 +/- 1.67 L/min/m2 of body surface area (P less than 0.005). Mixed venous oxygen tension (PvO2) increased from 28.4 +/- 4.3 to 41.2 +/- 5.2 mm of Hg (P less than 0.001). Pulmonary edema resolved, as determined on thoracic radiographs. Mixed venous oxygen tension correlated well with the cardiac index (r = 0.92; P less than 0.001). It was concluded that hydralazine administration caused a small decrease in end diastolic diameter (4.8 +/- 0.9 to 4.5 +/- 0.8 cm, P less than 0.05) and end systolic diameter (2.6 +/- 0.8 to 2.3 +/- 0.7 cm, P less than 0.05). Fractional shortening and heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of electroacupuncture on intraocular pressure and hemodynamic parameters in isoflurane anesthetized dogs

The effects of electroacupuncture (EA) on intraocular pressure (IOP) and hemodynamic parameters were evaluated in isoflurane anesthetized 10 (5 males, 5 females) normal mongrel dogs (8.1-9.8 kg, 6-8 years old). After determination of baseline IOP and hemodynamic parameters (cardiac index, systolic arterial pressure, diastolic arterial pressure, heart rate and systemic vascular resistance index), EA was applied at 3 acupoints (LI-4, LIV-3 and GB-37) for 20 min. After the EA treatment, IOP was significantly decreased in the both eyes (p<0.05). However, there were not significant differences in hemodynamic parameters between those of before and after EA treatment. From these results, the EA treatment at LI-4, LIV-3 and GB-37 would be considered one of the valuable methods for the IOP treatment in dogs.     

Intraocular pressure,specular microscopy,and prostaglandin E2 concentration in dogs with mature and hypermature cataract

This study aimed to evaluate and correlate intraocular pressure (IOP), endothelial cell density (CD), and hexagonality (HEX), and the aqueous humor prostaglandin E₂ (PGE₂) concentration in dogs with mature (MG, n = 8) and hypermature (HG, n = 8) cataracts. Eight laboratory beagles with no ocular abnormalities were included as a control group (CG). The IOP was measured using a digital applanation tonometer. Noncontact specular microscopy was used to evaluate CD and HEX. Samples of aqueous humor were used to determine prostaglandin E₂ concentration using enzyme‐linked immunoassay. Data were compared by anova and Bonferroni's multiple comparison test, and possible correlations among the PGE₂ aqueous concentration and corneal endothelium cell parameters were assessed by Person′s test (P < 0.05). Average values of IOP (P = 0.45) and CD (P = 0.39) were not significantly different between MG, HM, and CG. Average values of HEX were lower, and PGE₂ concentration was increased in the MG and HG in comparison with CG (P < 0.05); however, such parameters did not change significantly between MG and HG (P > 0.05). PGE₂ values did not correlate with IOP, CD, and HEX in any group (P > 0.05). Although there were a small number of dogs studied, our results demonstrated that cataract progression from mature to hypermature did not have a significant change in PGE2 aqueous concentration, IOP, corneal endothelial cell count, or morphology. In addition, PGE₂ concentration was not correlated with parameters of the corneal endothelium or IOP in dogs with mature or hypermature cataracts.     

Comparative hemodynamic effects of halothane and halothane-acepromazine at equipotent doses in dogs.

The purpose of this study was to compare the cardiovascular effects of halothane when used alone at increasing doses (1.2, 1.45 and 1.7 minimum alveolar concentration, MAC) to those produced with equipotent doses of halothane after potentiation of the anesthetic effect with acepromazine (ACP) sedation (45% reduction of halothane MAC). Six healthy mature dogs were used on three occasions. The treatments were halothane and intramuscular (IM) saline (1.0 mL), halothane and ACP (0.04 mg/kg IM), or halothane and ACP (0.2 mg/kg IM). Anesthesia was induced and maintained with halothane in oxygen and the dogs were prepared for the collection of arterial and mixed venous blood and for the determination of heart rate, systolic, diastolic and mean arterial pressure, mean pulmonary arterial pressure (PAP), central venous pressure and cardiac output. Following animal preparation the saline or ACP was administered and positive pressure ventilation instituted. Twenty-five minutes later the dogs were exposed to the first of three anesthetic levels, with random assignment of the sequence of administration. At each anesthetic level, measurements were obtained at 20 and 35 min. Calculated values included cardiac index, stroke index, left ventricular work, systemic vascular resistance, arterial oxygen content, mixed venous oxygen content, oxygen delivery and oxygen consumption. Heart rate was significantly higher with halothane alone than with both halothane-ACP combinations and was significantly higher with high dose ACP compared to low dose ACP. Systolic and mean blood pressures were lowest with halothane alone and highest with 0.2 mg/kg ACP, the differences being significant for each treatment. Oxygen uptake and PAP were significantly lower in dogs treated with ACP. It was concluded that ACP does not potentiate the cardiovascular depression that accompanies halothane anesthesia when the resultant lower dose requirements of halothane are taken into consideration.     

Minimum infusion rate and hemodynamic effects of propofol, propofol-lidocaine and propofol-lidocaine-ketamine in dogs

ObjectiveTo evaluate the effects of a constant rate infusion (CRI) of lidocaine alone or in combination with ketamine on the minimum infusion rate (MIR) of propofol in dogs and to compare the hemodynamic effects produced by propofol, propofol-lidocaine or propofol-lidocaine-ketamine anesthesia.Study designProspective, randomized cross-over experimental design.AnimalsFourteen adult mixed-breed dogs weighing 15.8 ± 3.5 kg.MethodsEight dogs were anesthetized on different occasions to determine the MIR of propofol alone and propofol in combination with lidocaine (loading dose [LD] 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) or lidocaine (LD 1.5 mg kg^?1, CRI 0.25 mg kg^?1 minute^?1) and ketamine (LD 1 mg kg^?1, CRI 0.1 mg kg^?1 minute^?1). In six other dogs, the hemodynamic effects and bispectral index (BIS) were investigated. Each animal received each treatment (propofol, propofol-lidocaine or propofol-lidocaine-ketamine) on the basis of the MIR of propofol determined in the first set of experiments.ResultsMean ± SD MIR of propofol was 0.51 ± 0.08 mg kg^?1 minute^?1. Lidocaine-ketamine significantly decreased the MIR of propofol to 0.31 ± 0.07 mg kg^?1 minute^?1 (37 ± 18% reduction), although lidocaine alone did not (0.42 ± 0.08 mg kg^?1 minute^?1, 18 ± 7% reduction). Hemodynamic effects were similar in all treatments. Compared with the conscious state, in all treatments, heart rate, cardiac index, mean arterial blood pressure, stroke index and oxygen delivery index decreased significantly, whereas systemic vascular resistance index increased. Stroke index was lower in dogs treated with propofol-lidocaine-ketamine at 30 minutes compared with propofol alone. The BIS was lower during anesthesia with propofol-lidocaine-ketamine compared to propofol alone.Conclusions and clinical relevanceLidocaine-ketamine, but not lidocaine alone, reduced the MIR of propofol in dogs. Neither lidocaine nor lidocaine in combination with ketamine attenuated cardiovascular depression produced by a continuous rate infusion of propofol.     

Expressions of estrogen receptors in the bovine corpus luteum: cyclic changes and effects of prostaglandin F2alpha and cytokines

Estrogen (E) exerts its function by binding to two intracellular estrogen receptors, ERalpha and ERbeta. Although ERs have been reported to be expressed in the bovine corpus luteum (CL), the mechanisms that control ER expression in the bovine CL are not fully understood. To determine the possible regulatory mechanisms of ERalpha and ERbeta that meditate distinct E functions, we examined 1) the changes in the protein expressions of ERs in the CL throughout the luteal phase and 2) the effects of prostaglandin (PG) F2alpha, tumor necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) on the expressions of ERs in cultured bovine luteal cells. Western blot analyses revealed that ERalpha and ERbeta proteins were expressed throughout the luteal phase. The ERalpha protein level was high at the early luteal (Days 2-3 after ovulation) and mid-luteal stages (Days 8-12) and was extremely low at the regressed luteal stage (Days 19-21). The ERbeta protein level increased from the early to developing luteal stage, remained at the same level at the mid-luteal stage and decreased thereafter. The ratio of ERbeta to ERalpha was higher in the regressed stage than in the other stages. Luteal cells obtained from mid-stage CLs (Days 8-12) were incubated with PGF2alpha (0.01-1 microM), TNFalpha (0.0145-1.45 nM) or IFNgamma (0.0125-1.25 nM) for 24 h. PGF2alpha and TNFalpha inhibited ERa and ERbeta mRNA expressions. IFNgamma suppressed ERbeta mRNA expression but did not affect the expression of ERalpha mRNA. However, the ERalpha and ERbeta protein levels were not affected by any of the above treatments. These data indicate that PGF2alpha, TNFalpha and IFNgamma regulate ERalpha and ERbeta mRNA expressions in bovine luteal cells. Moreover, the changes in the ERbeta/ERalpha ratio throughout the luteal phase suggest that ERalpha is associated with luteal maintenance. Therefore, a dramatic decrease in ERalpha at the regressed luteal stage could result in progression of structural luteolysis in the bovine CL.     

Endotoxin-induced changes in expression of cyclooxygenase isoforms in the lamellar tissue of extracorporeally haemoperfused equine limbs

Angiogenesis and sepsis-related equine laminitis have several features in common. Both events can be induced by endotoxin (lipopolysaccharide— LPS) and both are associated with increased expression of the enzyme cyclooxygenase (COX), of which two isoforms (COX-1 and COX-2) exist. To examine the causal relationship between LPS exposure and COX expression and to investigate the tissue distribution of COX in the LPS-exposed tissue, the technique of extracorporeal haemoperfusion of isolated equine forelimbs was utilized. Perfusion was performed for 10 hr under physiological conditions (control-perfused limbs, n = 5) and with addition of 80 ng/L of endotoxin (LPS-perfused limbs; n = 5). After perfusion, samples of lamellar tissue were collected from the dorsal aspect of the hoof wall. Additional control samples were collected from three non-perfused limbs. Immunohistochemical analysis was performed using antibodies against COX-1 and COX-2, and intensity of immunohistochemical staining was scored for each isoform. In the lamellar tissue of control- and LPS-perfused limbs, there was no significant difference in COX-1 staining intensity and distribution, whereas COX-2 expression was significantly increased in LPS-perfused limbs (especially in endothelial cells, fibroblasts and intravasal leucocytes as well as in epidermal basal cells at the base of the primary epidermal lamellae). These results suggest that COX-2 and its metabolites are involved in the initiation of pathological changes seen in sepsis-associated events such as sepsis-related laminitis. In such cases, COX-2 could therefore be an important therapeutic target; however, early therapy may be required as increase in COX-2 expression occurs within 10 hr after LPS exposure.     

The role of thromboxane A2 in regulating porcine basilar arterial tone

The aim of the present study was to clarify the participation of endogenous arachidonic acid (AA) metabolites in regulating porcine basilar, coronary, pulmonary and mesenteric arterial tones in vitro . A cyclooxygenase inhibitor, indomethacin, relaxed basilar artery but not other arteries examined. Quinacrine (a phospholipase A₂ inhibitor), OKY-046 (a thromboxane (TX) A₂ synthetase inhibitor) and ONO-3708 (a TXA₂/prostaglandin H₂ receptor antagonist) produced relaxation in basilar arteries with intact endothelium. Nordihydroguaiaretic acid (a lipoxygenase inhibitor) had no effect on the tone. The amount of TXB₂ (a stable metabolite of TXA₂) spontaneously released from porcine basilar arteries was 6–10 fold more than those from other arteries. Indomethacin and OKY-046 mostly inhibited the production of TXB₂. Endothelial denudation decreased indomethacin-induced relaxation and the amount of TXB₂. These results suggest that a vasoconstricting substance(s) is released from endothelial cells and possibly smooth muscle cells in porcine basilar arteries in vitro . The main constricting substance is proposed to be TXA₂. On the other hand, several arteries from peripheral vascular beds did not release this vasoconstricting substance.