Inhibition of PARP overactivation protects acute kidney injury of septic shock.

OBJECTIVE: To evaluate pathological lesions in New Zealand white rabbits with acute kidney injury (AKI) of septic shock and to explore the potential role of poly (ADP-ribose) polymerase (PARP) in regulating AKI development. MATERIALS AND METHODS: Endotoxic shock model in New Zealand white rabbits was first constructed. CVP (central venous pressure) was maintained at the baseline level by the saline administration. Rabbits were randomly assigned into sham group, LPS group, and LPS+3-AB group, respectively. Blood samples and kidney samples of rabbits were collected 4 h after LPS administration. Pathological kidney lesions were observed by HE (hematoxylin-eosin) staining and immunohistochemistry. Serum levels of renal damage markers (Scr, Cys-C, KIM-1, and NGAL) were detected by an automatic biochemical analyzer, immunoturbidimetry, and ELISA (enzyme-linked immunosorbent assay), respectively. Kidney energy metabolism changes (ATP, ADP, PCr, and NAD) were detected by HPLC (high performance liquid chromatography analysis). Western blot was conducted to detect protein expressions of NF-κB (nuclear factor-kappa B), TNF-α (tumor necrosis factor-α), ICAM-1 (intercellular cell adhesion molecule-1) and P-selectin in kidney tissues. RESULTS: Significant pathological lesions in kidney tissues and higher pathological grade were seen in the LPS group. Multiple PARP-positive nuclei were found in renal tubular cells at the junction of renal cortex and renal cortex in the LPS group. Serum levels of Scr, KIM-1, NGAL, and Cys-C were remarkably higher in the LPS group than those of sham group. HPLC results showed decreased levels of ATP, ADP, PCr, and NAD in kidney cortex of LPS group compared with those of sham group. Western blot results suggested that protein expressions of NF-κB, TNF-α, ICAM-1, and P-selectin were remarkably upregulated in kidney tissues of LPS group. 3-AB pretreatment, the PARP inhibitor, remarkably alleviated pathological lesions and inflammation induced by AKI. CONCLUSIONS: Inhibition of PARP overactivation alleviated pathological kidney lesions, improved kidney energy metabolism and inhibited inflammatory response resulted from AKI.

[Impact of blood eosinophils on clinical effect of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps].

Objective: To investigate the effect of blood eosinophils on clinical effect of endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: From March 2011 to March 2016, 72 cases with CRSwNP were treated by endoscopic sinus surgery in Department of Otorhinolaryngology Head and Neck Surgery, Peking University People's Hospital. The clinical records were retrospectively reviewed, and the cases were divided into eosinophilia elevated and non-elevated group according to blood eosinophils, and nasal polyps were evaluated for histopathology eosinophil count. Statistical analysis was performed to compare two groups' pre- and post-operative symptoms of VAS score, sinus computed tomography (CT) scans scores according to the Lund-Mackay system and the outcome of surgery. Both groups' factors that might have affected their outcome were analyzed by t-test, Chi square, Pearson Correlation Coefficient and Willcoxon rank sum test. Results: Seventy two cases were followed up from 24 to 78 months.The average follow-up time was 56 months. The VAS score in the eosinophilia elevated group (n=16) was higher than that in the non-elevated group(n=56), and the difference was statistically significant (11.44±7.13 vs 4.98±5.64, t=3.726, P<0.05). The control of symptoms in the peripheral blood eosinophilia elevated group was less than that in the non-elevated group, and the difference was statistically significant (Z=-1.979, P<0.05). There was a positive correlation between eosinophil counts in peripheral blood and tissues of 72 cases (r=0.429, P<0.05). Conclusion: There is a significant correlation between tissue and blood eosinophil counts, and eosinophilia group has poorer outcomes.

[The role of type 2 innate lymphoid cells in the pathogenesis of eosinophilic chronic rhinosinusitis with nasal polyps].

Objective: To investigate the type 2 innate lymphoid cells (ILC2s) in eosinophilic nasal polyps, non-eosinophilic nasal polyps and controls, and to compare the characteristics of ILC2s indifferent types of nasal polyp. Methods: Flow cytometric analysis was used to quantify the ILC2s and Th2 cells in tissues from 19 patients with chronic rhinosinusitis with nasal polyp (CRSwNP) and 6 controls. The patients were classified into two groups as eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) and non-eosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) based on eosinophil counts under hematoxylin-eosin staining. ILC2 and Th2 cell frenquencies, measured as a percentage of CD45(+) cells, were compared among ECRSwNP group (n=9), non-ECRSwNP group (n=10) and control group (n=6) using Mann-Whitney U test .The correlation between ILC2, Th2 cell frequencies and eosinophil count in tissues was analyzed using Pearson correlation coefficient. Results: ILC2 frequencies in ECRSwNP group were significantly higher than non-ECRSwNP group and controls ((0.051±0.025) vs (0.011±0.017), (0.051±0.025) vs (0.004±0.004), Z value was -3.185, -3.186, respectively, both P<0.05). There was no significant difference between ILC2 frequencies in non-ECRSwNP and controls ((0.011±0.017) vs (0.004±0.004), Z=-0.712, P=0.492). Th2 cell frequencies in ECRSwNP and non-ECRSwNP group were significantly higher than controls ((0.500±0.437) vs (0.106±0.102), (0.275±0.170) vs (0.106±0.102), Z value was -2.946, -2.278, respectively, both P<0.05). There was no significant difference between Th2 frequencies in non-ECRSwNP group and ECRSwNP group ((0.275±0.170) vs (0.500±0.437), Z=-1.306, P=0.211). ILC2 frequencies significantly correlated with Th2 cell frequencies (r=0.571, P=0.011) and tissue eosinophilia (r=0.579, P=0.009). Th2 cell frequencies significantly correlated with tissue eosinophilia (r=0.844, P=0.001). There was no significant association between ILC2 and allergic status. Conclusion: ILC2s are elevated in ECRSwNP, and not influenced by allergic status, suggesting that ILC2s play an important role in ECRSwNP without allergic diseases.

[Subjective and objective evaluation and correlation analysis of pre- and post- operation in patients with structural nasal obstruction].

Objective: To analyze the subjective and objective results and the correlation of nasal obstruction because of nasal structural variation pre and post operation, and to provide clinical evidence for surgery and curative effect. Methods: Three groups were included in this study: group 1 were 78 patients with structural rhinitis, group 2 were 72 patients with chronic sinusitis (without nasal polyp) and group 3 were healthy controls of 75 cases. Assessment of nasal obstruction was achieved by visual analog scale (VAS), and objective measurement was achieved by rhinomanometry and acoustic rhinometry. The first two minimum cross-sectional area of nasal cavity (MCA1, MCA2), their distances from the nostrils (MD1, MD2) and the nasal volume of 5 cm depth from the nostril (NV5) were recorded. The ratio of the parameters of the two sides of the nasal cavity was calculated respectively. Nasal resistance total (RT) and calculated right-left nasal resistance ratio (Rlr) were recorded. Patients of group 1 and group 2 accepted endoscopic surgery and received the above evaluation again at three months after surgery. Three groups were compared with statistical test. Results: The preoperative values of three groups (MCA1, MD1, MCA2, MD2, NV5, RT) showed no statistical significance (F value was 0.945, 0.245, 1.380, 0.036, 0.866, 1.651, respectively; all P>0.05), while their ratio had statistical differences except MD1 (F value was 5.242, 1.726, 4.882, 4.005, 5.066, 5.316; P=0.013, 0.199, 0.019, 0.024, 0.018, 0.011, respectively). Statistical results between the ratio of values (MCA1, MD1, MCA2, MD2, NV5, RT) and VAS of nasal obstruction of group 1 and group 2 showed significant positive correlations pre operation(r of group 1 value was 0.471, 0.418, 0.260, 0.324, 0.305, 0.459, respectively; r of group 2 value was 0.373, 0.403, 0.288, 0.366, 0.402, 0.249, respectively; all P<0.05). VAS scores pre and post operation of group 1 had statistically difference (t=35.122, P<0.05). Postoperative value of MD1, MD2 and RT among three groups had no statistical difference (F value was 0.178, 0.582, 0.905, respectively; all P>0.05). Postoperative value of MCA1, MCA2, NV5 among three groups had statistical difference (F value was 4.010, 5.126, 4.901, respectively; all P<0.05). Postoperative ratio of MCA1, MD1, NV5 and Rlr among three groups had no statistical difference (F value was 1.023, 0.944, 0.524, 0.996, respectively; all P>0.05). Postoperative ratio of MCA2 and MD2 among three groups had statistical difference (F value was 4.859, 4.357, respectively; all P<0.05). Conclusion: Severity of nasal obstruction is related to structural variation of nasal cavity and the purpose of surgery is to restore structural symmetry of bilateral nasal cavity.

[Rosenmüller valve during endoscopic dacryocystorhinostomy in treating refractory nasolacrimal duct obstruction].

OBJECTIVE: The objective of this study was to assess the efficacy of exposing Rosenmüller valve during endonasal endoscopic dacryocystorhinostomy (EES-DCR) in treating refractory nasolacrimal duct obstruction. METHODS: Thirty six patients (47 eyes) with refractory nasolacrimal duct obstruction were entered into this study, including 13 patients (15 eyes) underwent nasal lacrimal duct intubation before, 18 patients (26 eyes) with small lacrimal sac, 2 patients underwent DCR before, 1 patient with functional nasal lacrimal duct obstruction, 1 patient with lacrimal mucocele, 1 patient with nasal trauma. During the DCR, the bone window was enlarged as wide as possible and the valve of Rosenmüller was exposed. The intubation of the lacrimal apparatus was performed if the lacrimal sac was very small and the Rosenmüller valve was tight. Functional endoscopic sinus surgery and septoplasty were performed simultaneously if necessary. Postoperatively, each patient was assessed by the symptom and nasal endoscopy. RESULTS: The postoperative follow-up period ranged from 3 to 36 months. Thirty two patients(89.4%, 42/47 eyes) were cured, which presented as the disappearance of symptoms, the patency of the lacrimal ostium and the lacrimal duct irrigation was clear. One patient (2.1%, 1/47 eyes) was improved, which presented as the improvement of symptoms, a few hypertrophic scar around the lacrimal ostium and the lacrimal duct irrigation was clear. Four cases failed (8.5%, 4/47), which presented as symptomatic and obstruction of the lacrimal ostium. The total effective rate reached to 91.5%. No serious postoperative complications were found in all cases. CONCLUSIONS: To expose Rosenmüller valve during endoscopic DCR in treating patients with refractory nasolacrimal duct obstruction could obviously increase the operative success rate, fewer complications, with no facial surgical scar. It is an ideal way to treat the refractory nasolacrimal duct obstruction.

[Clinical evaluation about rhinoplasty of nasal cavity improving nasal obstruction in patients with structural variation].

Objective:To explore the long-term effect of rhinoplasty of nasal cavity improving nasal obstruction in patients with structural variation. Method:One hundred and six patients with structural rhinitis included this study whose assessment of nasal obstruction were achieved by visual analogue scale(VAS), and were divided into two groups: group1(n=56,VAS score >5), group 2(n=48,VAS score <5).They were measured by rhinomanometry and acoustic rhinometry recording the minimum cross-sectional area of nasal cavity(MCA), the distances from the nostrils(MD) and the nasal volume of 5 cm,2-5 cm,5-7 cm from the nostril(V5,V2-5,V5-7),then we calculated the ratio of the parameters of the two sides of the nasal cavity respectively, recorded nasal resistance and calculated Rlr. All patients were performed endoscopic rhinoplasty of nasal cavity and re-evaluated one-year later. Two groups were compared with statistical test.Result: The symptoms of twogroup patients improved satisfactorily after surgery. VAS scores and ratio of pre-operation of two groups had statistical differences except MD,V5-7,and group1 had more structural abnormalities compared with group 2.VAS scores and ratio of pre- and post-operation of group1 had statistically difference. Conclusion:Severity of nasal obstruction is related to structural variation of nasal cavity and the nasal plasty has certain clinical application value as its good long-term curative effects,the purpose of surgery is to restore symmetry of nasal cavity.

GRP78 promotes the invasion of pancreatic cancer cells by FAK and JNK.

The major characteristics of pancreatic cancer are its excessive local invasion and early systemic dissemination. The glucose-regulated protein is over-expressed in many human cancers including pancreatic cancer and correlated with invasion and metastasis in many cancers. To investigate the effect of Grp78 on the invasion of pancreatic cancer, we used western blot and Transwell assay. We found Grp78 is expressed at lower levels in capan-2 and higher expressed in MiaPaCa-2 cells, and Grp78 expression levels were correlated with the invasion potentials of tumor cells. Then,we increased the expression of Grp78 in capan-2 cells and decreased the expression of Grp78 in MiaPaCa-2 cells. We found that over-expression of Grp78 caused significant increase in the expression of TIMP-1, TIMP-2, MMP-14, MMP-2, and MMP-9 in Capan-2 cells. Consistently, knockdown of Grp78 decreased the expression of them in MiaPaCa-2 cells. Gelatin zymography showed Grp78 over-expression stimulated the activities of MMP-2 and MMP-9, while GRP78 knockdown reduced the activities of MMP-2 and MMP-9. Cytoskeleton staining showed that knockdown of Grp78 caused a marked increase in cytoskeleton F-actin stress fibers in MiaPaCa-2 cells. Consistently, GRP78 knockdown hyperactivated RhoA and inhibited significantly Rac activity. Grp78 over-expression decreases the RhoA and stimulated Rac activity. We also found that Grp78 modulated FAK and JNK signaling pathways. Over-expression of GRP78 in Capan-2 activated FAK and JNK. Finally, we demonstrated that knockdown of FAK by shRNA in combination with blockade of JNK signaling pathway with SP600125 completely inhibited GRP78-induced cancer cell invasion. GRP78 is involved in the regulation of pancreatic cancer invasion. FAK and JNK are the key downstream effectors of GRP78.

Kidney transplantation from cardiac death donors with terminal acute renal failure.

OBJECTIVES: Kidney transplantation from donation after cardiac death (DCD) donors with terminal acute renal failure (ARF) is not widely accepted due to concern about the organ quality. Here we report our initial clinical outcomes of kidney transplantation from DCD donors with ARF. MATERIALS AND METHODS: The results of 29 kidney transplants from ARF DCD donors were compared with those of 60 kidney transplants from non-ARF DCD donors performed at our center from August 2011 to March 2013. RESULTS: There was no difference in the incidence of delayed graft function and acute rejection between ARF and non-ARF kidneys (27.6% vs 16.7%, 10.3% vs 8.3%, respectively). Estimated glomerular filtration rate at 12 months was similar between ARF and non-ARF kidneys. With a mean follow-up of 18 months (range 7 to 26 months), actual patient and graft survival rates for ARF DCD recipients were 100% and 96.6%, respectively, which were similar to those of the control group of kidney transplants from non-ARF kidneys (98.3% and 95.0%). CONCLUSIONS: Kidneys from DCD donors with terminal ARF have excellent short-term outcomes and may represent another potential method to safely expand the donor pool.

Genetic diversity and classification of Oryza sativa with emphasis on Chinese rice germplasm.

Despite extensive studies on cultivated rice, the genetic structure and subdivision of this crop remain unclear at both global and local scales. Using 84 nuclear simple sequence repeat markers, we genotyped a panel of 153 global rice cultivars covering all previously recognized groups and 826 cultivars representing the diversity of Chinese rice germplasm. On the basis of model-based grouping, neighbour-joining tree and principal coordinate analysis, we confirmed the widely accepted five major groups of rice cultivars (indica, aus, aromatic, temperate japonica and tropical japonica), and demonstrated that rayada rice was unique in genealogy and should be treated as a new (the sixth) major group of rice germplasm. With reference to the global classification of rice cultivars, we identified three major groups (indica, temperate japonica and tropical japonica) in Chinese rice germplasm and showed that Chinese temperate japonica contained higher diversity than that of global samples, whereas Chinese indica and tropical japonica maintained slightly lower diversity than that present in the global samples. Particularly, we observed that all seasonal, drought-tolerant and endosperm types occurred within each of three major groups of Chinese cultivars, which does not support previous claims that seasonal differentiation exists in Indica and drought-tolerant differentiation is present in Japonica. It is most likely that differentiation of cultivar types arose multiple times stemming from artificial selection for adaptation to local environments.

Effect of inhaled MgSO4 on FEV1 and PEF in children with asthma induced by acetylcholine: a randomized controlled clinical trail of 330 cases.

OBJECTIVES: To determine the response of nebulized magnesium sulfate on the lung function of acetylcholine-induced asthma children. METHODS: Three hundred and thirty children of asthma with positive bronchial provocation test were randomly divided into three groups: magnesium sulfate, albuterol, and a combination of magnesium sulfate and albuterol. Lung function was compared between the three groups. RESULTS: Forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) as percentage over predicted at 10 min and 20 min in albuterol and combination group were significantly improved when compared to magnesium group. The changes in FEV1 and PEF expressed as absolute and percentage over predicted was not statistically significant from baseline to 20 min in magnesium, albuterol, and combination of magnesium sulfate and albuterol. There was no significant adverse effect observed during the present study. CONCLUSION: Nebulized magnesium sulfate alone has a bronchodilatory effect in Ach-induced asthmatic children. The combination of MgSO4 and albuterol did not has a synergistic effect.

Inflammatory myofibroblastic tumour of the maxillary sinus: CT and MRI findings.

AIM: To characterize the computed tomography (CT) and magnetic resonance imaging (MRI) findings of inflammatory myofibroblastic tumours (IMTs) of the maxillary sinus. MATERIALS AND METHODS: The imaging findings of eight patients with IMTs of the maxillary sinus were reviewed retrospectively. Of the eight patients, four patients underwent unenhanced and contrast-enhanced CT, and one patient underwent unenhanced CT only; three patients underwent unenhanced and contrast-enhanced MRI. RESULTS: Five cases of IMTs occurred in the left maxillary sinus, while three cases were right-sided. Four cases occupied the entire sinus, and the other four cases only partially occupied the sinus. Unenhanced CT images showed heterogeneous masses in four cases and a homogeneous mass in one case. One of the tumours showed some areas of calcification. T1-weighted MRI images showed isointense lesions. T2-weighted images showed mixed isointense and mild hyperintense lesions. All cases showed bone destruction and had infiltrated into the nasal fossa, orbit, infratemporal fossa, and other adjacent tissues. Seven cases showed mild to moderate heterogeneous enhancement on contrast-enhanced CT or T1-weighted MRI images. CONCLUSION: IMTs of the maxillary sinus can be characterized as a soft-tissue mass with bony destruction and infiltration of the adjacent tissues, with mild to moderate enhancement after the injection of contrast medium. CT and MRI can help to diagnose IMTs, determine the extent of the lesion and its relationship with adjacent tissues, and thus facilitate the prediction of surgical resectability.

Karyotype analysis of mithun (Bos frontalis) and mithun bull x Brahman cow hybrids.

We examined the cytogenetics of mithun (Bos frontalis), a domesticated version of the Asian gaur, and hybrids (F(1) generation) produced by artificial insemination of Brahman cows (Bos indicus) with mithun semen. Reproductive potential was also examined in the F(1) generation and a backcrossed heifer for utilization of heterosis. Metaphase chromosome spreads were examined by conventional staining and fluorescence in situ hybridization hybridized with the entire chromosome 1 of mithun as a specific probe. Chromosome 1 of mithun was found to be equivalent to Bos taurus chromosomes 2 and 28. The karyotype of the female mithun (N = 4) comprised 58 chromosomes, including 54 acrocentric and four large submetacentric chromosomes, without the four acrocentric chromosomes found in the domesticated species B. indicus. However, one of the four female mithuns with a normal mithun phenotype had an abnormal karyotype (2n = 59), indicating introgression from B. taurus or B. indicus. The F(1) karyotypes (N = 6, 3♂3♀) of the mithun bull × Brahman cow cross had 2n = 59, intermediate between their parents; they were consistent heterozygous carriers with a centric fusion involving rob(2;28), as expected. Two pronounced red signals were seen in the mithun karyotypes, three red signals in the mithun × Brahman hybrids, and four red signals in the Brahman cattle, in good agreement with centric fusion of bovine rob(2;28). The female backcross hybrid (N = 1) with 2n = 59 had a similar chromosome configuration to the F(1) karyotypes and had rob(2;28). Such female backcross hybrids normally reproduce; however, the F(1) bulls (N = 3) had not yet generated normal sperm at 24 months.

Electron microscopic examination of the viromatrix of Rana grylio virus in a fish cell line.

Rana grylio virus (RGV), a Ranavirus belonging to the family Iridoviridae, assembles in the viromatrix which is a factory for viral genome replication and particle assembly. Ultrastructural studies of the viromatrix will clarify the pathway of assembly. The viromatrix and quantitative changes in RGV infected epithelipma papulosum cyprini (EPC) cells, one of fish cell lines, were studied by electron microscopy. It was shown that viromatrices were adjacent to the nucleus, and the electron density was lower than that of the surrounding cytoplasm. The viromatrix contained virus particles with different forms, electron-dense materials and amorphous structures which included tubules and membranous materials. Tubules were often observed in direct continuity with empty capsids. Several bundles of intermediate filaments were seen alongside the viromatrix and crystalline aggregates. Large clusters of mitochondria occurred in proximity to viromatrix. A total of 990 cells profiles were examined. The results showed that 394 cells contained viromatrix: 89.3% contained one, and 10.7% contained two to four viromatrices. The number of viromatrices increased gradually and reached a peak at 16 h p.i. The viromatrix area at 24 h p.i. increased up to 7.4 +/- 0.69 microm(2) which was three-times lower than that at 6 h p.i. The number of empty capsids within viromatrix was generally more than that of "full" particles at different time points, and there was a strong positive correlation between them.

Gene therapy for Parkinson's disease: recent achievements and remaining challenges.

Gene therapy is the use of nucleic acids as drugs. Thus, ways had to be developed to deliver this new generation of drugs to target tissues. Various viral and non-viral vectors have been engineered to carry potentially therapeutic nucleic acids into diseased organs or target cells. The brain offers a particular challenge for gene delivery to its constituent cells: it is encased by the skull, separated from the general circulation by the blood brain barrier, and made up of mostly non-dividing cells. The skull limits direct injection of vectors into the brain, the blood brain barrier inhibits the easy entry of vectors injected into the bloodstream, and post mitotic target cells restrict what type of vector can be used to deliver genes to the brain. We will discuss the main challenges faced by gene delivery to the brain, i.e. immune responses to the delivery vectors and therapeutic transgenes and length of duration of the therapy specifically as applied to Parkinson's disease. We will also discuss therapeutic strategies, which could be implemented to treat Parkinson's disease, and the models in which they have been tested.

[Intranasal endoscopic treatment of chronic sinusitis in children].

OBJECTIVE: To explore the curative effect of endoscopic sinus surgery (ESS) and the factors associated with surgery effect for treating children with chronic sinusitis. METHOD: Thirty-one children with a median age of 10 years (range 5-14 years) who suffered from chronic sinusitis or/and nasal polyps and were operated via ESS from May 1996 to January 1999 were retrospectively analyzed. RESULT: According to the therapeutic evaluation standard (ESS-1997, Haikou), twelve cases (38.7%) were completely cured, fifteen cases (48.4%) were improved and four children (12.9%) showed no change with a general effective rate of 87.1% without any severe operative complication. CONCLUSION: The results suggested ESS is a safe and effective method in the treatment of children with chronic sinusitis or/and nasal polyps. Furthermore, meticulous postoperative endoscopic care and medication are also important for securing optimal long-term results.

[Distribution, content and action site of leucine-enkephalin in pulmonary artery wall of rat and rabbit].

Using immunohistochemical method to investigate the distribution of peptidergic fibers in the pulmonary artery wall of SD rat, L-enkephalin immunoreactive (L-ENK ir) fibers were easily demonstrated. The contents of L-ENK in pulmonary artery of rat and rabbit measured by radioimmunoassay were respectively 439.18 +/- 30.52 and 29.9 +/- 1.4 (pg/mg of wct tissue). Contraction of superfused strips of pulmonary artery of rabbit could be evoked by parameter I electric field stimulation. The response was blocked by alpha-receptor antagonist phentolamine. Alpha 2-receptor antagonist Yohimbine enhanced the response in small doses (0.06-0.12 mumol/L), while inhibited in large (3.2 mumol/L). The contraction could also be enhanced when the artery strips were preincubated with naloxone. After the alpha-receptors were blocked with phentolamine, stronger contraction could still be evoked by parameter II electric field stimulation and the response was not affected by naloxone. L-ENK had no effect on the contraction evoked by exogenous NE. The present experiments demonstrate that enkephalin presented in the pulmonary artery wall are released by electric field stimulation. Enkephalin may reduce the release of NE from sympathetic nerve endings via opioid receptors and inhibit the contraction response.