Efficacy of Radiation Therapy for the Treatment of Sialocele in Dogs.

BACKGROUND: Sialocele is a collection of saliva that has leaked from a damaged salivary gland or duct and is surrounded by granulation tissue. Surgery is the recognized first-line treatment. Recurrence rate after surgery is 5-14%. Salivary gland tissue is very sensitive to radiation therapy (RT). HYPOTHESIS/OBJECTIVES: Radiation therapy will be useful for the treatment of sialocele. The aims were to characterize response rate and clinical course of dogs with sialocele treated with RT and to determine a starting dose for clinical use. ANIMALS: Eleven dogs with sialocele. METHODS: Retrospective study of response and outcome after RT. RESULTS: All dogs had cervical sialocele. Seven dogs (63.6%) were treated with 3 weekly fractions of 4 Gray (Gy); (total dose, 12 Gy). Three dogs (27.3%) received 4 fractions of 4 Gy (16 Gy) and 1 dog received 5 fractions of 4 Gy (20 Gy) on a Monday-Wednesday-Friday schedule. Six dogs (54%) achieved a complete response (CR), and 5 dogs (45%) achieved a partial response (PR). Three dogs had progression of their sialocele 2, 3, and 9 months after RT; all three had received 12 Gy initially and 2 received 2 additional fractions of 4 Gy (cumulative total dose, 20 Gy) and subsequently achieved remission for >2 years. CONCLUSIONS AND CLINICAL IMPORTANCE: Radiation therapy is useful for the treatment of recurrent sialocele refractory to surgical management and a minimum total dose of 16 or 20 Gy in 4 Gy fractions appears effective.

[Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study]. / Kombinierte Anwendung von Strahlentherapie und DNS Tumor Vakzine zur Behandlung des oralen malignen Melanoms beim Hund: Eine Pilotstudie.

Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

Multimodal therapeutic approach and interdisciplinary challenge for the treatment of unresectable head and neck squamous cell carcinoma in six cats: a pilot study.

Feline head and neck squamous cell carcinoma (SCC) is a loco-regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials.

[New concepts in human oncology: is it possible to use them in veterinary medicine as well?]. / Neue Konzepte in der humanen Onkologie: Können sie in der Veterinärmedizin eingesetzt werden?

In human oncology, novel targeted therapy focusing on monoclonal antibodies and tyrosine kinase inhibitors has become an attractive anticancer strategy. The introduction of antiangiogenetic drugs and metronomic chemotherapy has also increased the therapeutic arsenal. Chemotherapy still plays a key role in the treatment of many tumors affecting dogs and cats. However, novel anticancer strategies (including tyrosine kinase inhibitors and monoclonal antibodies, as well as antiangiogenetic treatments) are becoming relevant in veterinary medicine, too. The goal of this review is to describe new therapeutic strategies for cancer treatment in veterinary medicine, including less well-known chemotherapeutic drugs.

[A new total knee arthroplasty with physiologically shaped surfaces. Part 2: First clinical results]. / Eine neuartige Kniegelenksendoprothese mit physiologischer Gelenkform. Teil 2: Erste klinische Ergebnisse.

The human medial tibial plateau is concave, whereas the lateral tibial plateau is convex. In a normal knee, the convex femoral condyles roll and glide on the tibia during the standing phase of walking. The designs of most commercially available knee prostheses do not take this morphological feature into consideration. The novel design of the AEQUOS G1 knee replacement prosthesis is based on the natural anatomy of the knee joint, with a convex lateral tibia plateau and a sagittal offset of the medial and lateral compartments. Following extensive development and testing, initial clinical results of the AEQUOS G1 prosthesis in a mulitcenter study are presented. From Mai 2005 to March 2007, 158 patients in 4 clinics underwent total knee arthroplasty with the AEQUOS G1 and agreed to participate in the study. Patients were evaluated preoperatively and at 3, 6 and 12 months of follow-up using a standardized protocol that included the American Knee Society Score (AKSS), the Oxford Knee Score (OKS) and the Visual Analog Scale (VAS) for pain. After 3 months, 151 patients appeared for follow up appointments, after 6 months, 134, and after 12 months, 127. The mean range of motion preoperatively was 97.0 degrees (+/-19.9 degrees ) and 107.5 degrees (+/-15.9 degrees ) 12 months after surgery. The AKSS, as well as the modified OKS, significantly improved (p<0.0001) from preoperative scores of 98.8 (+/-35.8) and 37.3 (+/-6.9) points, respectively, to 165.8 (+/-34.1) and 21.9 (+/-7.8) points, preoperatively, and 12 months postoperatively. The VAS score significantly decreased (p<0.001) from 7.4 (+/-1.8) points preoperatively to 1.9 (+/-2.2) points 12 months postoperatively.One implant was revised because of arthrofibrosis and another due to patellar luxation. Two patients required revision because their implants revealed malalignement with ligamentous instability. No infections, aseptic loosening or other implant-specific complications were observed at this early follow-up. Good clinical results were observed at early follow-up with the AEQUOS G1 knee arthroplasty. However, longer follow-up is necessary for a general evaluation of the implant.

Primary pulmonary spindle cell tumour (haemangiopericytoma) in a dog.

Haemangiopericytoma is a soft tissue sarcoma believed to originate from pericytes. These tumours are commonly located on the skin and subcutaneous tissue of dogs and are most commonly found on the limbs. To the authors' knowledge, primary lung haemangiopericytomas have not been previously described in dogs. This case report describes the diagnostic evaluation and treatment of a primary haemangiopericytoma of the lung in a 10-year-old male, neutered, Siberian husky dog. Staging of the tumour was performed using a computed tomography scan of the thorax and a computed tomography-guided fine-needle aspiration biopsy of the lesion. Treatment was a right caudal lobectomy from a right lateral approach. No regional lymph node changes were noted on computed tomography or intraoperative assessments. Histopathology confirmed a spindle cell tumour that stained positive for vimentin and negative for desmin and S-100.

Detection of high-energy phosphates in cortical bone as an indicator of bone healing and remodelling: use of a rabbit model.

UNLABELLED: PURPOSE; To study high-energy phosphates in cortical bone through experiments on inbred white New Zealand rabbits. METHODS: Tibial fractures were induced in 80 rabbits and then stabilised by screw osteosynthesis. After 3 (group A; n=40) or 7 days (groups B; n=40), the defective tissue was covered by local muscle flaps. At increasing intervals (from 1 to 16 weeks), the screws were removed and the animals were euthanised (n=8 per group). The bone was removed and analysed histomorphologically; adenosine triphosphate (ATP) levels were determined by high-performance liquid chromatography. RESULTS: The mean ATP concentration in healthy cortical bone at 16 weeks was 0.092 (standard error, 0.009) nmol/mg dry mass, which was significantly higher than that in the group with delayed healing: 0.081 (0.011) nmol/mg in group A and 0.005 (0.001) nmol/mg in group B (paired t test, p<0.05). Earlier healing led to lower rates of necrosis (0 vs 38; groups A vs B) and osteomyelitis. CONCLUSION: Early muscle-flap coverage can revascularise the cortical bone, which is reflected in the higher ATP content in the cortical bone measured by high-performance liquid chromatography. Measuring changes of ATP levels can help investigate the metabolism of the pathological bone.

[Locally recurrent rectal carcinoma]. / Lokoregionäres Rezidiv des Rektumkarzinoms.

There is no doubt that surgical treatment with curative intent is warranted in patients with recurrent colorectal cancer. This is also true for locally recurrent rectal cancer. Operative procedures are demanding but may be curative if complete excision can be achieved. Preoperative radiochemotherapy has helped to improve resectability, but operative morbidity is still high. Procedure-related mortality on the other hand is low, at around 3%, and 25% 5-year survival can be expected after complete excision.

Laparoscopic management of hydronephrosis in a woman with rare genitourinary anomalies: unicornous uterus, contralateral agenesis of the kidney, and contralateral ectopic ovary in the groin.

A 40-year-old woman had infected right-sided hydronephrosis and rare genitourinary anomalies-a dextroposed unicornous uterus-as the cause of the hydronephrosis, which had to be mobilized laparoscopically by dissecting the scar tissue. Furthermore, the patient had left-sided agenesis of the kidney and a left-sided ectopic ovary with a rudimentary tube in the inner inguinal canal.

Thermodiffusion for the quantification of tissue perfusion in skeletal muscle--clinical evaluation in standardized traumatological procedures with tourniquet and potential application in the diagnosis of compartment syndrome.

The quantification of tissue perfusion in different parenchymal organs like liver, kidney, and brain by means of thermodiffusion has recently been validated experimentally and was introduced into clinical practice. Traumatology and plastic surgery deal as well with issues of microcirculation. Therefore, it was the aim of this study to validate thermodiffusion for use in skeletal muscle. Eighteen patients were studied during knee arthroscopic procedures that utilized a tourniquet. A thermodiffusion probe was inserted in the tibialis anterior muscle of the side under treatment. Measurement started before the initiation of limb ischemia (by tourniquet) and continued throughout the procedure until tissue perfusion returned to normal values postoperatively. Furthermore, an example of clinical applicability of this technique is given by monitoring muscle tissue perfusion in 3 patients with imminent compartment syndrome. Preoperative values of muscle tissue perfusion in the patients undergoing arthroscopic procedures were 17.74 +/- 4.27 ml/min 100 g. After initiation of tourniquet perfusion quickly decreased to 3.59 +/- 3.53 ml/min 100 g. Upon reperfusion tissue perfusion increased to values above normal for a few minutes and then returned to preischemic values of 20.86 +/- 7.01 ml/min 100 g. There was no significant difference between pre- and postoperative values (P=0.154) but tissue perfusion during tourniquet was significantly reduced (P=0.0001). In 3 patients presenting with the clinical signs of imminent compartment syndrome, thermodiffusion measurement was applied and showed microcirculatory impairment of different degrees. Fasciotomy was followed by a prompt increase of muscle microcirculation to levels slightly above normal. In summary, valid and stable measurements of tissue perfusion in skeletal muscle by means of thermodiffusion are possible under clinical circumstances. Thermodiffusion allows for on-line monitoring of muscle microcirculation, e.g., in compartment syndrome. The clinical potential of thermodiffusion measurements in trauma surgery needs further prospective evaluation.

Laser doppler flow imaging of open lower leg fractures in an animal experimental model.

PURPOSE: Open lower leg fractures are frequently associated with severe soft tissue damage, followed by osteomyelitis. Using an animal experimental model, we investigated the effect of timing of coverage of a tibial fracture with a local muscle flap. METHODS: 80 rabbits had a tibial fracture induced in a standardised fashion, which was stabilised by screw osteosynthesis. After 3 (group A; n=40) and 7 days (group B; n=40), respectively, the tissue defect was covered by a local gastrocnemius flap. In increasing intervals from 1 to 2, 4, 8, and 16 weeks, the rabbits from each group were killed and the bone fracture was analysed histomorphologically. Cortical microcirculation was measured by 2-channel laser doppler flowmetry. RESULTS: Muscle flaps after 3 days improved perfusion significantly as compared with 7 days (24 Flux [standard error, 5 Flux] versus 10 Flux [3 Flux]; baseline, 1.4 Flux). Group A animals also displayed a lower rate of necrosis (0 versus 38). The incidence of osteomyelitis was higher in group B than in group A (24% versus 0%). CONCLUSION: Laser doppler flowmetry was proven to be a reliable, minimally invasive means for identifying avital tissue, leading to reduction in the loss of vital bone tissue in experimental settings.

Function of SERCA mediated calcium uptake and expression of SERCA3 in cerebral cortex from young and old rats.

Previous work on peripheral sympathetic neurons indicated that a decline in sarco/endoplasmic reticulum calcium ATPase (SERCA) function occurs with advancing age. Therefore, an age-related decline in mechanisms controlling intracellular calcium homeostasis could contribute to altered neuronal function and/or degeneration. In this study we sought to extend the findings on peripheral neurons and to detect possible age-related declines in SERCA function and expression of SERCA3 in central neurons from cerebral cortex from young (6-month) and old (20-month) rats. Functional studies compared ATP-dependent 45Ca(2+)-uptake into microsomes and plasma membrane vesicles (PMVs). We and found no significant difference in 45Ca(2+)-uptake between microsomes or PMVs between young and old animals. On the other hand expression of SERCA3 mRNA in rat cerebral cortex showed a significant decline with advancing age. However, comparison of SERCA3 protein content did not reveal a corresponding decline; implying that SERCA mRNA turnover rates may be greater in the younger group. Although the present work with rat cerebral cortex does not indicate an age-related decline in SERCA function, previous work from our laboratory on sympathetic nerves and by others on the hippocampus indicate such a decline. In light of our previous and current studies, aging may affect calcium homeostatic mechanisms in central and peripheral autonomic neurons differently.

[Angle- and rotation-stable internal fixation of proximal humerus fractures with the humerus fixator plate. Early clinical experience with a newly developed implant]. / Die winkel- und rotationsstabile Osteosynthese proximaler Humerusfrakturen mit der Humerus-Fixateurplatte. Erste klinische Erfahrungen mit einem neu entwickelten Spezialimplantat.

INTRODUCTION: The Humerus Fixator Plate is presented as a new implant for angle- and rotation-stable internal fixation for the operative treatment of proximal humerus fractures at the surgical neck. METHODS: In an ongoing two-centre study, 47 patients were treated with the new implant. To date, 31 patients had clinical and radiological postoperative follow-up examinations with a mean interval of 10 months (range: 6-14 months). RESULTS: In 46 patients (97.9%), complete angle and rotational stability was achieved without limiting the range of motion or requiring immobilization. Good pain relief was obtained in 43 patients (91.5 %), and 3 patients (6.4%) showed moderate pain relief following surgery. There was one implant failure. Utilizing the Constant-Raw score (without any correction factors), a mean result of 82.8 points (range: 46-100 points) was ascertained. The majority of the patients (87.1%) achieved "excellent" or "good" clinical results. X-ray analysis revealed no non-union nor humerus head necrosis. In 4 cases (12.9%), protrusion of a humerus head screw was observed which mandated removal of the implant. CONCLUSION: The first clinical investigations of the novel Humerus Fixator Plate are encouraging and provide essential advances in the treatment of unstable proximal humerus fractures.

Adrenergic nerves compensate for a decline in calcium buffering during ageing.

1. The ubiquitous involvement of intracellular calcium ([Ca2+]i) in multiple neuronal pathways has led investigators to suggest that dysfunction of calcium homeostasis may be the primary mediator of age-related neuronal degeneration. Recently, it was shown that sympathetic neurones from superior cervical ganglion (SCG) of aged rats demonstrate decreased sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA) function and that aged neurones are more dependent upon mitochondria to control K+-evoked [Ca2+]i transients. 2. Therefore, in the present study we investigated age-related changes in ATP-dependent calcium pumps of plasma membrane Ca2+-ATPase (PMCA) and SERCA in acutely dissociated SCG cells from Fischer-344 rats aged 6 and 20 months. To distinguish between PMCA and SERCA pump activity, we applied the Ca2+-ATPase blocker vanadate and measured rates of recovery of K+-evoked [Ca2+]i transients by fura-2 microfluorometry. 3. Young SCG cells showed a biphasic response to vanadate over the vanadate concentration range (0.01-100 microM); however, old SCG cells showed only a single response over the same concentration range. Additionally, old SCG cells showed a greater sensitivity to Ca2+-ATPase blockade by vanadate. 4. The contribution of mitochondrial calcium uptake to regulate [Ca2+]i was also investigated. To measure the impact of mitochondrial calcium uptake, PMCAs and SERCAs were blocked with vanadate (100 microM) and extracellular sodium was replaced with tetraethylammonium (TEA) to block Na+/Ca2+-exchange. Treated SCG cells showed a decline of 50% in rate of recovery of [Ca2+]i in both 6- and 20-month-old cells; however, this effect did not vary with age. 5. These data suggest that there is an age-related decline in function of SERCAs, with an increased reliance on PMCAs to control high K+-evoked [Ca2+]i transients. In addition, there appears to be no age-related change in the capacity of the mitochondria to restore [Ca2+]i transients to basal levels.

SERCA function declines with age in adrenergic nerves from the superior cervical ganglion.

1. Intracellular calcium is a universal second messenger integrating numerous cellular pathways. An age-related breakdown in the mechanisms controlling [Ca2+]i homeostasis could contribute to neuronal degeneration. One component of neuronal calcium regulation believed to decline with age is the function of sarco/endoplasmic reticulum calcium ATPase (SERCA) pumps. 2. Therefore we investigated the impact of age on the capacity of SERCA pumps to control high (68 mM) [K+]-evoked [Ca2+]i-transients in acutely dissociated superior cervical ganglion (SCG) cells from 6- and 20-month-old Fisher-344 rats. Calcium transients were measured by fura-2 microfluorometry in the presence of vanadate (0.1 microM) to selectively block plasma membrane calcium ATPase (PMCA) pumps, dinitrophenol (100 microM) to block mitochondrial calcium uptake and extracellular sodium replaced with tetraethylammonium to block Na+/Ca2+-exchanger, thus forcing the neuronal cells to rely on SERCA uptake to control [Ca2+]i homeostasis. 3. In the presence of these calcium buffering blockers, the rate of recovery of [Ca2+]i was significantly slower and time to recover to approximately 90% of resting [Ca2+]i was significantly greater in SCG cells from old (20 months) compared with young (6 months) animals. 4. This age-related change in the recovery phase of [K+]-evoked [Ca2+]i-transients could not be explained by differences in the sensitivity of SCG cells to the calcium buffering blockers, as no age-related difference in basal [Ca2+]i was observed. 5. These studies illustrate that when rat SCG cells are forced to rely on SERCAs to buffer [K+]-evoked [Ca2+]i-transients, an age-related decline in SERCA function is revealed. Such age-related declines in calcium regulation coupled with neuronal sensitivity to calcium overload underscore the importance of understanding the components of [Ca2+]i homeostasis and the functional compensation that may occur with advancing age.

A molecular basis of cell death in olfactory epithelium.

When the membrane receptor Fas binds its ligand, Fas ligand (FasL), an apoptotic cascade is initiated in the cell bearing the Fas receptor. The same can be said about the tumor necrosis factor receptor-1 (TNFR1) and its ligand, TNF-alpha. In this study we have shown that the mRNAs of both sets of ligands and receptors, Fas/FasL and TNF-alpha/TNFR1, were present in unperturbed olfactory epithelium. Fas and FasL were shown by immunohistochemistry and by Western blots of bulbectomized animals to be in the neurons and in some non-neuronal (microvillar) cells of unperturbed rat olfactory epithelium. Addition of either FasL or TNF-alpha to organotypic cultures of fetal rat olfactory epithelium resulted in a significant increase in the number of apoptotic bodies after 4-6 hours. These data raise the possibility that either or both ligand-receptor pairs participate in cell death in the olfactory epithelium.

Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells.

The multidrug resistance protein MRP1 functions as an ATP-dependent conjugate export pump and confers multidrug resistance. We cloned MRP2 (symbol ABCC2), a MRP family member localized to the apical membrane of polarized cells. Stable expression of MRP2 in transfected human embryonic kidney (HEK-293) and Madin-Darby canine kidney (MDCK) cells was enhanced by inhibitors of histone deacetylase. In polarized MDCK cells, both rat and human MRP2 were sorted to the apical plasma membrane. An antibody raised against the amino terminus of rat MRP2 recognized the recombinant protein on the apical surface of nonpermeabilized cells, providing direct evidence for the extracellular localization of the amino terminus of MRP2. ATP-dependent transport by recombinant human and rat MRP2 was measured with membrane vesicles from stably transfected cells. The Km value of human MRP2 was 1.0 +/- 0.1 microM for leukotriene C4 and 7.2 +/- 0.7 microM for 17beta-glucuronosyl estradiol; the Km values of human MRP1 were 0.1 +/- 0.02 microM for leukotriene C4 and 1.5 +/- 0.3 microM for 17beta-glucoronosyl estradiol. Thus, the conjugate-transporting ATPases MRP2 and MRP1 differ not only by their domain-specific localization but also by their kinetic properties. Drug resistance conferred by recombinant MRP2 was studied in MDCK and HEK-293 cells using cell viability assays. Expression of human and rat MRP2 enhanced the resistance of MDCK cells to etoposide 5.0-fold and 3.8-fold and to vincristine 2.3- and 6.0-fold, respectively. Buthionine sulfoximine reduced resistance to these drugs. Human MRP2 overexpressed in HEK-293 cells enhanced the resistance to etoposide (4-fold), cisplatin (10-fold), doxorubicin (7.8-fold), and epirubicin (5-fold). These results demonstrate that MRP2 confers resistance to cytotoxic drugs.

Improved exercise performance following lung volume reduction surgery for emphysema.

Lung volume reduction surgery (LVRS) for emphysema has been suggested to improve patient lung function and activity. The short-term impact of LVRS on exercise performance was evaluated using maximal and submaximal steady-state exercise testing in 27 patients with severe hypoxemic chronic obstructive pulmonary disease (COPD), along with measurements of patient function, dyspnea, and quality of life. LVRS significantly improved exercise performance, due to ventilatory improvements associated with increased ventilatory reserve, enhanced tidal volume recruitment, and improved alveolar ventilation. Preoperative measurements of ventilatory reserve and dead space ventilation during exercise testing were closely associated with improved exercise performance. Improvements in patient dyspnea, walk distances, and quality of life also occurred following LVRS and were associated with improvements in exercise performance. Surgical mortality from LVRS was low (4%), but short-term all-cause mortality was increased (19%). Short-term mortality was associated with reduced expiratory muscle strength and markedly elevated dead space ventilation. We conclude that LVRS produces significant improvements in exercise performance, dyspnea, and quality of life in selected patients with COPD. Physiologic prediction of patients most likely to survive for an extended period and have significant benefit following LVRS may also be possible.

Adrenergic nerve smooth endoplasmic reticulum calcium buffering declines with age.

Calcium buffering capacity declines with age in sympathetic nerves of rat tail artery. To test whether smooth endoplasmic reticulum (SER) calcium buffering declines with age, effects of two SER calcium-ATPase inhibitors on norepinephrine release and intracellular calcium were determined. Thapsigargin or cyclopiazonic acid caused a significant increase in stimulation-evoked norepinephrine release from 6 month tail arteries with much less effect in 20 months. In isolated superior cervical ganglion cells, the rate of rise of calcium with K+-depolarization increased only in young cells with either cyclopiazonic acid or thapsigargin, with no effect in the old. In young cells, cyclopiazonic acid significantly influenced time to peak, rate of decline, and time to basal of K+-evoked calcium transients, but had no effect in old cells. Thapsigargin caused a significant increase in rate of decline in young, but not old, cells. These differential effects suggest an age-related decline in function of SER calcium buffering mechanisms in the sympathetic nervous system causing older nerves to become more reliant on mitochondria to buffer calcium.

Sex differences in the effects of 17 beta-estradiol on vascular adrenergic responses.

The in vitro effects of 17 beta-estradiol on vascular responses to adrenergic nerve stimulation were studied in perfused tail arteries from age-matched male and female rats. Nerve stimulation resulted in vasoconstriction that was greater in male arteries. Addition of 17 beta-estradiol (3 x 10(-5) M) reduced the vasoconstrictor responses in both male and female arteries, but the reduction was significantly greater in the females. Gonadectomy of the animals for 1 month prior to the experiment did not alter the in vitro responses to 17 beta-estradiol in either males or females. 17 beta-Estradiol (10(-6) - 3 x 10(-5) M) also relaxed perfused tail arteries precontracted with KCl (50 mM); however the relaxation was not different between males and females, either intact or gonadectomized. Stimulation-evoked release of noradrenaline from adrenergic nerves of perfused tail arteries was measured, but no differences were found between males and females, nor was release modified by in vitro exposure to 17 beta-estradiol (10(-5) M). These results suggest that 17 beta-estradiol acts directly on postjunctional mechanisms to relax tail arteries of either sex. The effect of the hormone on arteries constricted by adrenergic nerve stimulation, however, is greater in females compared to males.