Distribution and pathological features of pancreatic, ampullary, biliary and duodenal cancers resected with pancreaticoduodenectomy.

BACKGROUND: Pancreatic cancer (PC) has the worst survival of all periampullary cancers. This may relate to histopathological differences between pancreatic cancers and other periampullary cancers. Our aim was to examine the distribution and histopathologic features of pancreatic, ampullary, biliary and duodenal cancers resected with a pancreaticoduodenectomy (PD) and to examine local trends of periampullary cancers resected with a PD. METHODS: A retrospective review of PD between January 2000 and December 2012 at a public metropolitan database was performed. The institutional ethics committee approved this study. RESULTS: There were 142 PDs during the study period, of which 70 cases were pre-2010 and 72 post-2010, corresponding to a recent increase in the number of cases. Of the 142 cases, 116 were for periampullary cancers. There were also proportionately more PD for PC (26/60, 43% pre-2010 vs 39/56, 70% post-2010, P = 0.005). There were 65/116 (56%) pancreatic, 29/116 (25%), ampullary, 17/116 (15%) biliary and 5/116 (4%) duodenal cancers. Nodal involvement occurred more frequently in PC (78%) compared to ampullary (59%), biliary (47%) and duodenal cancers (20%), P = 0.002. Perineural invasion was also more frequent in PC (74%) compared to ampullary (34%), biliary (59%) and duodenal cancers (20%), P = 0.002. Microvascular invasion was seen in 57% pancreatic, 38% ampullary, 41% biliary and 20% duodenal cancers, P = 0.222. Overall, clear margins (R0) were achieved in fewer PC 41/65 (63%) compared to ampullary 27/29 (93%; P = 0.003) and biliary cancers 16/17 (94%; P = 0.014). CONCLUSIONS: This study highlights that almost half of PD was performed for cancers other than PC, mainly ampullary and biliary cancers. The volume of PD has increased in recent years with an increased proportion being for PC. PC had higher rates of nodal and perineural invasion compared to ampullary, biliary and duodenal cancers.

Factores de riesgo en el fracaso de la reparación quirúrgica del prolapso de suelo pelviano / Risk Factors in the Failure of Surgical Repair of Pelvic Organ Prolapse

Introducción: La cirugía del prolapso de órganos pelvianos (POP) presenta resultados variables de recurrencia y complicaciones. El objetivo es analizar nuestros resultados para conocer los factores que se asocian al fracaso anatómico y funcional tras la corrección con malla del POP. Material y métodos: Estudio retrospectivo de 69 pacientes intervenidas de POP en nuestro centro. Se registró la edad, IMC, número de partos, cirugía pélvica previa, menopausia, calidad de vida, incontinencia urinaria, frecuencia-urgencia asociada y presencia de POP de alto grado, compartimentos reparados, mallas usadas, uretrosuspensión e histerectomía vaginal durante la cirugía y las complicaciones. Se evaluó a las pacientes al mes, a los 6 y 12 meses, considerando fracaso de la cirugía si se extruyó la malla, si la paciente no estaba satisfecha o si recidivó. Se describe la muestra, se analizan la relación de las variables analizadas mediante análisis univariante (Chi cuadrado y U Mann-Whitney) y se estudia qué variables pueden tener valor predictivo en el fracaso de la reparación (regresión logística múltiple). Resultados: En 17 casos la cirugía se consideró fracaso al año de seguimiento. El IMC (29,6±2,03 vs 27,1±3,32), número de partos (3,4±0,71 vs 2,8±1,88), la menopausia, la presencia de frecuencia-urgencia y el número de mallas se asociaron al fracaso del tratamiento. Las variables independientes predictivas de fracaso según la regresión logística fueron: IMC, número de partos y la presencia de urgencia-incontinencia. Conclusión: El sobrepeso-obesidad, el número de partos previos y la sintomatología de incontinencia-urgencia preexistente son factores asociados al fracaso anatómico y funcional tras la reparación del POP (AU)

Introduction: Pelvic organ prolapse (POP) surgery has variable results of recurrence and complications. We have aimed to analyze our outcomes in order to know the factors associated with anatomical and functional failure in POP surgery. Material and methods: A retrospective study of 69 patients who underwent POP surgery at our hospital was performed. Registered variables were: Age, BMI, number of deliveries, previous pelvic surgery, menopause, quality of life, urinary incontinence, associated frequency-urgency symptoms, high POP stage, vaginal compartments repaired, type of mesh, urethro-suspension and vaginal hysterectomy during POP surgery and its complications. Patients were evaluated at 1, 6 and 12 months post-surgery. The technique was considered as failed when relapse or mesh erosion occurred and when the patient is not satisfied or there was relapse. The sample is described, analyzing the relationship of the variables studied by univariate analysis (Chi square and Mann-Whitney U test) and a study was made of which variables may have predictive value in the failure of the repair (multiple logistic regression). Results: Surgery failed in 17 patients during the follow-up at one year. BMI (29.6±2.03 vs 27.1±3.32), delivery number (3.4±0.71 vs. 2.8±1.88), menopause, frequency- urgency symptoms and number of vaginal compartments repaired were associated with treatment failure although only BMI, delivery number and frequency-urgency symptoms were defined as independent predictive variables when the logistic regression was carried out. Conclusions: Overweightness-obesity, previous delivery number and frequency-urgency symptoms before surgery are factors associated to anatomical and functional failure after POP repair (AU)

[Risk factors in the failure of surgical repair of pelvic organ prolapse]. / Factores de riesgo en el fracaso de la reparación quirúrgica del prolapso de suelo pelviano.

INTRODUCTION: Pelvic organ prolapse (POP) surgery has variable results of recurrence and complications. We have aimed to analyze our outcomes in order to know the factors associated with anatomical and functional failure in POP surgery. MATERIAL AND METHODS: A retrospective study of 69 patients who underwent POP surgery at our hospital was performed. Registered variables were: Age, BMI, number of deliveries, previous pelvic surgery, menopause, quality of life, urinary incontinence, associated frequency-urgency symptoms, high POP stage, vaginal compartments repaired, type of mesh, urethro-suspension and vaginal hysterectomy during POP surgery and its complications. Patients were evaluated at 1, 6 and 12 months post-surgery. The technique was considered as failed when relapse or mesh erosion occurred and when the patient is not satisfied or there was relapse. The sample is described, analyzing the relationship of the variables studied by univariate analysis (Chi square and Mann-Whitney U test) and a study was made of which variables may have predictive value in the failure of the repair (multiple logistic regression). RESULTS: Surgery failed in 17 patients during the follow-up at one year. BMI (29.6±2.03 vs 27.1±3.32), delivery number (3.4±0.71 vs. 2.8±1.88), menopause, frequency- urgency symptoms and number of vaginal compartments repaired were associated with treatment failure although only BMI, delivery number and frequency-urgency symptoms were defined as independent predictive variables when the logistic regression was carried out. CONCLUSIONS: Overweightness-obesity, previous delivery number and frequency-urgency symptoms before surgery are factors associated to anatomical and functional failure after POP repair.

Tratamiento combinado con radioterapia externa y hormonoterapia en los pacientes con cáncer de próstata localmente avanzado: factores predictivos de toxicidad genitourinaria / Combined External Radiotherapy and Hormone Therapy in Patients with Locally Advanced Prostate Cancer: Predictive Factors of Genitourinary Toxicity

Introducción: una opción de tratamiento del cáncer de próstata localmente avanzado es la radioterapia combinada con la ablación androgénica. Revisamos los resultados de eficacia y toxicidad del tratamiento combinado en un grupo de pacientes tratados con esta terapia combinada en nuestra institución. Material y método: estudio retrospectivo de 80 pacientes con cáncer prostático localmente avanzado tratados con radioterapia externa y hormonoterapia neoadyuvante (dos meses) y adyuvante (24 meses). Se realiza un estudio descriptivo de las variables clínico-patológicas y de los efectos secundarios. Evaluamos la respuesta al tratamiento mediante el PSA nadir y recidiva bioquímica. Analizamos la toxicidad aguda y crónica genitourinaria, intentando establecer qué factores influyen en su aparición mediante análisis uni y multivariante (regresión logística múltiple). Resultados: la media de edad fue 68 ± 5,81 años, el PSA inicial 20,05 ±1 6,27 ng/ ml y el volumen prostático medio 43,7 ± 27,57 cc. El 33% fueron estadio T3a y el 66% T3b. El Gleason fue < 7 en el 39%, 7 en el 46% y ≥ 8 en el 15%. Tras un seguimiento medio de 44,4 meses se detectó recidiva bioquímica en tres casos. La toxicidad aguda postirradiación genitourinaria apareció en el 90% (35% tardía) y gastrointestinal en el 75% (32% tardía). El análisis univariante muestra relación entre el volumen prostático y los síntomas urinarios previos con la toxicidad genitourinaria aguda y crónica. Estos se confirman como factores predictivos independientes de toxicidad geniturinaria en el análisis de regresión logística. Conclusiones: la hormono-radioterapia es una opción válida para el tratamiento del cáncer localmente avanzado con resultados óptimos a corto plazo, aunque no está exenta de efectos secundarios. La sintomatología urinaria previa y el volumen prostático pueden predecir la toxicidad genitourinaria (AU)

Introduction: Radiotherapy and androgen deprivation are an established treatment option for locally advanced prostate cancer. We evaluate outcomes in efficacy and toxicity for patients treated with this combined therapy at our institution. Methods: A retrospective study of 80 patients with locally advanced prostate cancer treated with radiotherapy combined with neo-adjuvant (2 months) and adjuvant (24 months) androgen deprivation. We studied the clinical variables and side effects. We evaluated treatment outcomes using PSA nadir and biochemical failure, and recorded acute and late gastrointestinal and urinary toxicity. We assessed the correlation between clinical variables and urinary toxicity by means of univariate and multivariate analyses (multiple logistic regression). Results: The mean patient age was 68 ± 5.81 years; the initial PSA was 20.05 ± 16.27 ng/ ml and the mean prostate volume 43.7 ± 27.57 cc. The clinical stage was T3a in 33% and T3b in 66%. The Gleason score was <7 in 39%, 7 in 46% and ≥8 in 15%. The mean follow-up was 44.4 months and biochemical failure was observed in 3 cases. Acute urinary toxicity was recorded in 90% of the patients (chronic in 35%) and acute gastrointestinal toxicity in 75% (late in 32%). In a univariate analysis, prostate volume and urinary symptoms were statistically correlated to acute and late urinary toxicity. Both prostate volume and urinary symptoms were independently associated with an increase in urinary toxicity in the logistic regression analysis. Conclusions: Hormone-radiotherapy is a valid option to locally treat advanced prostate cancer with optimal short-term outcomes, although it is not devoid of side effects. Prostate volume and urinary symptoms before treatment can predict genitourinary toxicity (AU)

[Combined external radiotherapy and hormone therapy in patients with locally advanced prostate cancer: predictive factors of genitourinary toxicity]. / Tratamiento combinado con radioterapia externa y hormonoterapia en los pacientes con cáncer de próstata localmente avanzado: factores predictivos de toxicidad genitourinaria.

INTRODUCTION: Radiotherapy and androgen deprivation are an established treatment option for locally advanced prostate cancer. We evaluate outcomes in efficacy and toxicity for patients treated with this combined therapy at our institution. METHODS: A retrospective study of 80 patients with locally advanced prostate cancer treated with radiotherapy combined with neo-adjuvant (2 months) and adjuvant (24 months) androgen deprivation. We studied the clinical variables and side effects. We evaluated treatment outcomes using PSA nadir and biochemical failure, and recorded acute and late gastrointestinal and urinary toxicity. We assessed the correlation between clinical variables and urinary toxicity by means of univariate and multivariate analyses (multiple logistic regression). RESULTS: The mean patient age was 68 ± 5.81 years; the initial PSA was 20.05 ± 16.27 ng/ ml and the mean prostate volume 43.7 ± 27.57 cc. The clinical stage was T3a in 33% and T3b in 66%. The Gleason score was <7 in 39%, 7 in 46% and ≥8 in 15%. The mean follow-up was 44.4 months and biochemical failure was observed in 3 cases. Acute urinary toxicity was recorded in 90% of the patients (chronic in 35%) and acute gastrointestinal toxicity in 75% (late in 32%). In a univariate analysis, prostate volume and urinary symptoms were statistically correlated to acute and late urinary toxicity. Both prostate volume and urinary symptoms were independently associated with an increase in urinary toxicity in the logistic regression analysis. CONCLUSIONS: Hormone-radiotherapy is a valid option to locally treat advanced prostate cancer with optimal short-term outcomes, although it is not devoid of side effects. Prostate volume and urinary symptoms before treatment can predict genitourinary toxicity.

The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2.

Bone morphogenetic proteins (BMPs) have been widely investigated for their clinical use in bone repair and it is known that a suitable carrier matrix to deliver them is essential for optimal bone regeneration within a specific defect site. Fused deposited modeling (FDM) allows for the fabrication of medical grade poly epsilon-caprolactone/tricalcium phosphate (mPCL-TCP) scaffolds with high reproducibility and tailor designed dimensions. Here we loaded FDM fabricated mPCL-TCP/collagen scaffolds with 5 microg recombinant human (rh)BMP-2 and evaluated bone healing within a rat calvarial critical-sized defect. Using a comprehensive approach, this study assessed the newly regenerated bone employing micro-computed tomography (microCT), histology/histomorphometry, and mechanical assessments. By 15 weeks, mPCL-TCP/collagen/rhBMP-2 defects exhibited complete healing of the calvarium whereas the non-BMP-2-loaded scaffolds showed significant less bone ingrowth, as confirmed by microCT. Histomorphometry revealed significantly increased bone healing amongst the rhBMP-2 groups compared to non-treated scaffolds at 4 and 15 weeks, although the % BV/TV did not indicate complete mineralisation of the entire defect site. Hence, our study confirms that it is important to combine microCt and histomorphometry to be able to study bone regeneration comprehensively in 3D. A significant up-regulation of the osteogenic proteins, type I collagen and osteocalcin, was evident at both time points in rhBMP-2 groups. Although mineral apposition rates at 15 weeks were statistically equivalent amongst treatment groups, micro-compression and push-out strengths indicated superior bone quality at 15 weeks for defects treated with mPCL-TCP/collagen/rhBMP-2. Consistently over all modalities, the progression of healing was from empty defect

Priority assessment of patients for elective general surgery: game on?

BACKGROUND: Clinical priority assessment criteria (CPAC) are used to generate a score by which patients are prioritized and rationed for elective surgery. It is widely believed that surgeons elevate scores to ensure their patients' acceptance for elective surgery, colloquially called gaming. The purpose of the present paper was therefore to investigate whether there was a temporal trend to an increase in the assigned priority score from the inception of CPAC to the present. METHODS: Priority and weighted inlier equivalent separations (WIES) scores between 23 April 1999 and 23 July 2002 were collected for elective general surgical cases at Auckland Hospital. A total of 5440 cases was retrospectively analysed using multiple regression techniques. Priority score was included as the dependent variable and time as an independent variable. Any change in case complexity over that period was accounted for by including the WIES score as a covariate. Multiple regression was undertaken for the combined surgeons and for individuals. RESULTS: The combined model was statistically significant but accounted for only 17% of the priority score variance. An increase of one WIES unit leads to an increase of 2.7 in priority score (P=0.0001). The relationship of priority score with time was dependent on the surgeon performing the prioritization. However, only half the surgeons had individual models that indicated gaming. CONCLUSIONS: The results show that gaming is occurring but that not all surgeons participate in this. The difference between surgeons' participation in gaming is a potential source of practice variation in the prioritization process.

Inhibition of nitric oxide activity by arginine analogs in human renal arteries.

BACKGROUND: Plasma levels of endogenous guanidine compounds are increased in various pathologic conditions, including chronic renal failure. In the present study we tested the effects of some of these compounds on basal and stimulated nitric oxide activity in human renal arteries. METHODS: Rings from human renal arteries were obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ baths for isometric recording of tension. We then studied the effects of N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine [ADMA]), aminoguanidine (AG), and methylguanidine (MG) on artery rings under basal and stimulated conditions. RESULTS: In precontracted arteries, L-NMMA (1 micromol/L to 1 mmol/L) and ADMA (1 micromol/L to 3 mmol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations [EC50] = 13.3 micromol/L and 17.5 micromol/L, respectively; Emax = 15+/-4% and 17+/-4% of the response to 100 mmol/L KCl, respectively). Aminoguanidine (0.01 to 3 mmol/L) and MG (0.01 to 3 mmol/L) produced endothelium-independent contractions (Emax = 9+/-3% and 16+/-2% of the response to 100 mmol/L KCl, respectively). L-arginine (1 mmol/L) but not D-arginine (1 mmol/L) prevented the contractions by L-NMMA and ADMA, but did not change contractions induced by AG and MG. In precontracted arteries, the relaxation to acetylcholine was decreased but not abolished by L-NMMA and ADMA. The remaining relaxation was reduced by charybdotoxin (0.1 mol/L) and tetraethylammonium (1 mmol/L). CONCLUSIONS: The results demonstrate that L-NMMA and ADMA reduce basal and stimulated nitric oxide activity in human renal arteries. An increase in the plasma concentrations of methylarginines associated with renal disease should be considered as a risk factor for endothelial dysfunction and abnormal vasomotor tone in human renal arteries.

Inhibition of neuroeffector transmission in human vas deferens by sildenafil.

Sildenafil (0.1 - 30 microM), a cyclic GMP phosphodiesterase 5 (PDE 5) inhibitor, induced inhibition of electrically evoked contractions of ring segments of human vas deferens from 34 vasectomies. Zaprinast (0.1 - 100 microM), another PDE 5 inhibitor, and the nitric oxide (NO) donor sodium nitroprusside (SNP) (0.1 - 100 microM) had no effect on neurogenic contractions. The inhibition induced by sildenafil was not modified by the inhibitor of guanylate cyclase 1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one (ODQ) (1 - 30 microM) but it was abolished by the K(+) channel blockers tetraethylammonium (TEA, 1 mM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM). Sildenafil, zaprinast and SNP did not affect the contractions induced by noradrenaline. SNP (10 microM) caused elevation of cyclic GMP levels that was potentiated by sildenafil (10 microM) and zaprinast (100 microM). ODQ (10 microM) inhibited the increase in cyclic GMP. Sildenafil inhibits adrenergic neurotransmission in human vas deferens. The inhibition is not related to accumulation of cyclic GMP but is probably due to activation of prejunctional large-conductance Ca(2+)-activated K(+) channels.

Effects of antidepressants in adrenergic neurotransmission of human vas deferens.

OBJECTIVES: To evaluate the effects of sertraline, fluoxetine, and amitriptyline on the contractile responses of the human vas deferens muscle elicited by norepinephrine, electrical field stimulation, and KCl, because the therapeutic action of antidepressants may be accompanied by sexual dysfunction related to the contractility of the vas deferens smooth muscle. METHODS: Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of sertraline, fluoxetine, and amitriptyline on the neurogenic and agonist-induced contractile responses. RESULTS: Amitriptyline caused concentration-dependent inhibition of neurogenic and norepinephrine-induced contractions. In contrast, only the highest concentration (10(-5) M) of sertraline and fluoxetine reduced the adrenergic contractions. The dihydropyridine calcium antagonist nifedipine (10(-6) M) completely prevented the inhibitory effect of sertraline and fluoxetine on neurogenic and norepinephrine-induced contractions but did not change the inhibition caused by amitriptyline. Sertraline, fluoxetine, and amitriptyline (all at 10(-5) M) attenuated contractions elicited by KCl and reduced contractions induced by CaCl(2) in KCl-depolarized preparations. CONCLUSIONS: The results indicate that sertraline and fluoxetine inhibit vas deferens motility through inhibition of Ca(2+) entry, with no effect on the adrenergic receptors, and amitriptyline acts as an adrenoceptor antagonist and inhibitor of the entry of calcium.

V2-receptor-mediated relaxation of human renal arteries in response to desmopressin.

The effects of deamino-8-D-arginine vasopressin (desmopressin), a V2 receptor antidiuretic agonist, were studied in isolated rings from branches of renal arteries obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ bath chambers for isometric recording of tension. In precontracted rings with norepinephrine (10(-6) to 3 x 10(-6) mol/L), desmopressin (10(-11) to 3 x 10(-7) mol/L) caused endothelium-dependent relaxation (81%+/-4% reversal of the initial contraction in arteries with endothelium; 20%+/-4% in arteries without endothelium; P < .05). The relaxation to desmopressin in rings with endothelium was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the inhibitor of nitric oxide synthase NG-nitro-L-arginine methyl ester (10(-4) mol/L). Two V1 receptor antagonists (a peptidic and a nonpeptidic) had no effect on desmopressin-induced relaxation. However, V2 receptor antagonists (three peptidic and a nonpeptidic) reduced significantly (P < .05) the maximal response to desmopressin. The results of this study show that desmopressin exerts powerful endothelium-dependent relaxation of human renal arteries, probably through stimulation of V2-like receptors that may bring about the release of dilating prostaglandins.

Vasopressin receptors involved in adrenergic neurotransmission in the circular muscle of the human vas deferens.

We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced contractions and abolished the induction of phasic activity by vasopressin in the presence of KCl. The results demonstrate that vasopressin, in addition to its direct contractile effects, strongly potentiates contractions of human vas deferens elicited by adrenergic stimulation. Both the direct and indirect effects of vasopressin appear to be mediated by vasopressin V1 receptor stimulation and are independent of Ca2+ entry through dihydropyridine Ca2+ channels.

Effects of vasopressin on human renal arteries.

The effects of vasopressin were studied in isolated rings from branches (2-3 mm in external diameter) of human renal arteries obtained from 18 patients undergoing nephrectomy for non-obstructive neoplasia. In arterial rings under resting tension, vasopressin produced concentration-dependent and endothelium-independent contractions with an EC50 of 9.1 X 10(-10) molL-1. The vasopressin V1 receptor antagonist d(CH2)Tyr(Me)AVP (10(-6) molL-1) displaced the control curve to vasopressin 564-fold to the right in a parallel manner. In precontracted arterial rings and previously treated with the V1 antagonist (10(-6) molL-1) vasopressin caused endothelium-independent relaxation. The relaxation to vasopressin was reduced significantly by indomethacin (10(-6) molL-1) and unaffected by the V1/V2 receptor antagonist desGly d(CH2)5-D-Tyr(Et)ValAVP(10(-6) molL-1) or by NG-nitro-L-arginine methyl ester (10(-4) molL-1). These observations indicate that vasopressin is primarily a constrictor of human renal arteries by V1-receptor stimulation. Vasopressin causes prostaglandin-mediated dilation of human renal arteries only if V1-receptor blockade is present. The effects of vasopressin on human renal arteries may be relevant in those clinical situations characterized by increased plasma vasopressin levels.

Reactivity of human deferential artery to constrictor and dilator substances.

The present study was designed to investigate general morphology and the response of human deferential artery to constrictor and dilator substances with special emphasis on endothelium-dependent responses. Human deferential artery segments were obtained from patients undergoing radical cystectomy (n = 7), suprapubic prostatectomy (n = 6), or radical prostatectomy (n = 6). Light microscopy revealed that human deferential artery is of muscular type, and fluorescence microscopy showed a dense adrenergic innervation. Paired rings, one normal and the other de-endothelialized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Vasopressin, endothelin, serotonin, and potassium chloride induced endothelium-independent contractions, whereas norepinephrine and electrical field stimulation caused frequency-dependent contractions that were of greater magnitude in arteries denuded of endothelium. In precontracted arterial rings, acetylcholine and substance P induced endothelium-dependent relaxations. In contrast, papaverine and sodium nitroprusside caused concentration-dependent relaxations that were similar in the presence and in the absence of endothelium. NG-nitro-L-arginine methyl ester (10(-4) M), an inhibitor of nitric oxide synthase, potentiated the responses to norepinephrine in artery rings with endothelium, nearly abolished the acetylcholine-induced relaxation, and attenuated the relaxation induced by substance P. incubation with methylene blue (10(-5) M), an inhibitor of guanylate cyclase, completely prevented the relaxation induced by acetylcholine in arteries with endothelium. The results of this study indicate that the human deferential artery has a dense adrenergic innervation and marked ability to contract or relax in response to different agonists. Some of these responses are in part endothelium dependent and mediated through release of nitric oxide. These morphological and pharmacological observations could play an important role in regulating flow or pressure of blood that arrives to the vas deferens.

Contractile responses of human deferential artery and vas deferens to vasopressin.

We studied the effects of vasopressin on isolated rings of human deferential artery and vas deferens (prostatic portion) obtained from patients undergoing radical cystectomy (n = 11) or prostatectomy (n = 10). Ring segments of artery or vas deferens were studied in organ bath experiments at optimal resting tension. In artery rings, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 4.5 x 10(-10) M. The presence of NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), an inhibitor of nitric oxide synthase, did not change significantly (P > 0.05) the vasopressin-induced contraction. In ring preparations of the prostatic part of the vas deferens, vasopressin induced phasic contractions with an EC50 of 7.0 x 10(-9) M. The vasopressin V1 receptor antagonist, d(CH2)5Tyr(Me)AVP (10(-8) and 10(-6)), displaced to the right in parallel the control curve to vasopressin in artery and vas deferens rings. These results indicate that vasopressin exerts a powerful constrictor action on human deferential artery and vas deferens by direct stimulation of V1 receptors. It is concluded that the deferential artery may dampen the passage of blood to the vas deferens in circumstances characterized by increased plasma vasopressin levels.

The human deferential artery: endothelium-mediated contraction in response to adrenergic stimulation.

The human vas deferens receives its blood supply from the deferential artery, a long vessel which usually arises from the superior vesical artery. To date no information is available on the responsiveness of this artery to adrenergic stimulation. In the present work the effects of electrical field stimulation and noradrenaline were studied isometrically in rings of human deferential artery obtained from patients undergoing radical cystectomy (n = 7) or prostatectomy (n = 10). Electrical field stimulation (1-8 Hz, 20 V, 0.25 ms for 30 s) caused frequency-dependent contractions that were abolished by guanethidine, tetrodotoxin or prazosin. Noradrenaline (10(-7)-10(-4) M) induced concentration-dependent contractions with an EC50 of 1.3 x 10(-5) M. The increases in tension induced by electrical field stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. The inhibitor of nitric oxide synthesis, NG-nitro-L-arginine methyl ester (10(-4) M), potentiated the responses to electrical field stimulation and noradrenaline in artery rings with endothelium. The results indicate that the human deferential artery has a marked ability to contract in response to adrenergic stimulation; they also suggest that the endothelium may have an inhibitory effect on adrenergic responses due, at least in part, to the release of endothelial nitric oxide. These effects could play an important role in regulating blood flow to the vas deferens.