Algorithm for early discharge after total thyroidectomy using PTH to predict hypocalcemia: prospective study.

PURPOSE: Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine whether postoperative parathyroid hormone (PTH) levels predict hypocalcemia in order to design an algorithm for early discharge. METHODS: We present a prospective study including patients who underwent total thyroidectomy. Hypocalcemia was defined as serum ionized calcium < 1.09 mmol/L or clinical evidence of hypocalcemia. PTH measurement was performed preoperatively and at 1, 3, and 6 h postoperatively. The percent decline of preoperative values was calculated for each time point. RESULTS: One hundred and six patients were included. Thirty-six (33.9%) patients presented hypocalcemia. A 50% decline in PTH levels at 3 h postoperatively showed the highest sensitivity and specificity to predict hypocalcemia (91 and 73%, respectively). No patients with a decrease <35% developed hypocalcemia (100% sensitivity), and all patients with a decrease >80% had hypocalcemia (100% specificity). CONCLUSIONS: PTH determination at 3 h postoperatively is a reliable predictor of hypocalcemia. According to the proposed algorithm, patients with less than 80% drop in PTH levels can be safely discharged the day of the surgery.

[Indications for sternotomy in thyroid surgery. Evolution over 20 years' experience]. / Evolution des indications de la sternotomie en chirurgie thyroïdienne. A propos d'une expérience de 20 ans.

From October 1984 to August 2005, 11,452 thyroidectomies were performed; 52 (0.45%) required a sternotomy. The patients included 32 women and 20 men. Sternotomy was total in 27 patients (52%) and partial in 25 (48%). Thirty patients (58%) had a benign goitre with intrathoracic extension, and 22 patients (42%) had thyroid malignancy. In 8 cases, the procedure was a reintervention. There were no post-operative deaths. Complications directly related to the sternotomy occurred in four patients (10%) and included one subcutaneous abscess, two cases of chylothorax (one requiring re-operation), and one pneumothorax. One patient developed a tight pseudoarthrosis of the sternotomy at eighteen months which caused neither pain nor functional disability. In comparing the first with the second decade of this study, we find that the incidence of sternotomy has not changed but that the indications have evolved. Initially sternotomy was indicated for benign intrathoracic goitres. More recently, thyroidectomy for malignancy, particularly in cases of re-operation, has been the major indication. Sternotomy is only rarely indicated in thyroid surgery. It adds moderately to hospital stay but does not increase morbidity when compared to the cervical approach.

[Impact of laparoscopy on the management of adrenal diseases. A retrospective study of 220 patients]. / Evolution de la prise en charge de la pathologie surrénalienne depuis l'avènement de la laparoscopie. Une étude rétrospective de 220 patients.

OBJECTIVE: Soon after its introduction in 1992, laparoscopic adrenalectomy became the gold standard in the surgical management of most adrenal tumors. The aim of this study was to assess the influence of laparoscopy on surgical indications. PATIENTS AND METHODS: Between 1994 and 2003, 220 adrenalectomies were performed, 179 among them by a laparoscopic approach. There were 137 females and 83 males. The mean age was 53 years (range 15-83 years). RESULTS: The indications of adrenalectomy were: Cushing syndrome 18%, pheochromocytoma 31%, Conn syndrome 16%, incidentaloma 21%, and malignant tumours 13%. Laparoscopic approach was performed in 81% of the cases and the conversion rate was 11%. There were 3 postoperative deaths (2 after laparoscopy). The mean hospital stay was 7.6 days in the laparoscopic group, and 13.6 days in the open surgery group. CONCLUSIONS: This study is consistent with the findings of the literature supporting that there are no indications for the open procedure in case of small benign lesions. The video-asisted adrenalectomy had not changed the management of the adrenal incidentaloma. Today, the laparoscopic approach seems to be adapted also for malignant disease.

Extra-gastrointestinal stromal tumour--semiology and clinical therapy peculiarities.

The gastrointestinal stromal tumor with extragastrointestinal location are very infrequent. We often diagnose them when they show a big size. Their bening or malignant nature is difficult to fix. The best histological parameters to evaluate their prognosis are a high cellularity, the tumor-like necrosis presence and having more than two mitosis per fifty high-power fields. We introduce an asyntomatic patient's case by a routine echographical control for chronic hepatitis by C virus, that has been diagnosed of a mesentery tumor. The patient has been treated surgically. The inmunohistological study of the tumor had confirmed a stromal gastrointestinal tumor. The showed case's analysis and the considered bibliography suggest some clinical discoveries characteristic of this entity. The histogenesis of these neoplasias are examined and made up to date and the usefulness of the new medication to control check the tumor-like progress is emphasized.

Complicaciones de la tiroidectomía total / Complications of total Thyroidectomy

La tiroidectoimía total es realizada con relativa frecuencia para el tratamiento tanto de patología maligna como en casos específicos de patología benigna de la glándula tiroides. La cifra de complicaciones varía en las distintas series publicadas. El objetivo de este trabajo es determinar las características y el porcentaje de complicaciones postoperatorias de la tiroidectomía total....La tiroidectomía total, realizada por cirujanos entrenados en la especialidad, es un procedimiento seguro y con una morbilidad aceptable

U-46619-induced potentiation of noradrenergic constriction in the human saphenous vein: antagonism by thromboxane receptor blockade.

OBJECTIVE: We investigated the potentiating effect of U-46619, a synthetic analogue of thromboxane A(2) (TXA(2)), on the adrenergic responses in human saphenous vein. METHODS: Saphenous vein rings were obtained from 35 patients undergoing coronary artery bypass surgery. The rings were suspended in organ bath chambers for isometric recording of tension. RESULTS: U-46619 (10(-10)-3 x 10(-7) mol/l) produced concentration-dependent and endothelium-independent contractile responses. U-46619 (10(-10) mol/l) potentiated the contractions elicited by electrical stimulation and potassium chloride, and produced leftward shifts of the concentration-response curve for noradrenaline. The TXA(2) receptor antagonist SQ-30741 (10(-8) mol/l) prevented the potentiation evoked by U-46619. The dihydropyridine calcium antagonist nifedipine (10(-6) mol/l) did not affect the potentiation of electrical stimulation and noradrenaline induced by U-46619, but abolished the potentiation of U-46619 on KCl-induced contractions. CONCLUSIONS: U-46619 facilitates sympathetic neurotransmission and potentiates constrictor effects of noradrenaline in human saphenous veins through stimulation of TXA(2) receptors. These effects are independent of calcium entry through dihydropyridine calcium channels.

Residues Y429 and Y463 of the human CD5 are targeted by protein tyrosine kinases.

The human CD5 lymphocyte cell surface co-receptor modulates activation and differentiation responses mediated by the antigen-specific receptor of T and B cells. CD5 is phosphorylated following lymphocyte activation; however, the exact sites and kinases involved are yet to be determined. Jurkat T cell transfectants expressing tyrosine-mutated CD5 molecules have been used to show that residues Y429 and Y463 are targeted in vivo by protein tyrosine kinases following cell stimulation with anti-CD3 mAb or pervanadate. This is in agreement with data from direct in vitro kinase assays using purified recombinant Lck and Fyn protein tyrosine kinases. The analysis of Lck- and CD3-deficient Jurkat cells shows that tyrosine phosphorylation of CD5 requires Lck activity. We propose that T cell activation mediates CD5 tyrosine phosphorylation at residues Y429 and Y463 mainly through the activation of Lck.

Genomic organization of the human CD5 gene.

CD5 is a member of the family of receptors which contain extracellular domains homologous to the type I macrophage scavenger receptor cysteine-rich (SRCR) domain. Here, we compare the exon/intron organization of the human CD5 gene with its mouse homologue, as well as with the human CD6 gene, the closest related member of the SRCR superfamily. The human CD5 gene spans about 24.5 kb and consists of at least 11 exons. These exons are conserved in size, number, and structure in the mouse CD5 homologue. No evidence for the biallelic polymorphism reported in the mouse could be found among a population of 100 individuals of different ethnic origins. The human CD5 gene maps to the Chromosome (Chr) 11q12.2 region, 82 kb downstream from the human CD6 gene, in a head-to-tail orientation, a situation which recalls that reported at mouse Chr 19. The exon/intron organization of the human CD5 and CD6 genes was very similar, differing in the size of intron 1 and the number of exons coding for their cytoplasmic regions. While several isoforms, resulting from alternative splicing of the cytoplasmic exons, have been reported for CD6, we only found evidence of a cytoplasmic tailless CD5 isoform. The conserved structure of the CD5 and CD6 loci, both in mouse and human genomes, supports the notion that the two genes may have evolved from duplication of a primordial gene. The existence of a gene complex for the SRCR superfamily on human Chr 11q (and mouse Chr 19) still remains to be disclosed.

Relaxation induced by cGMP phosphodiesterase inhibitors sildenafil and zaprinast in human vessels.

BACKGROUND: Sildenafil is currently used in the treatment of erectile dysfunction. However, assessment of direct effects of sildenafil on coronary arteries and on arteries used as coronary grafts is unknown. This study was designed to investigate the effects of sildenafil on contracted human coronary, internal mammary, and radial arteries obtained from multiorgan donors. The observations were extended to forearm veins. Zaprinast was included in this study for comparison. METHODS: Segments of left coronary, internal mammary, and radial arteries, and forearm veins were obtained from 16 multiorgan donors. Vascular rings were suspended in organ bath chambers and isometric tension was recorded. Then the effects of sildenafil, zaprinast, and sodium nitroprusside on precontracted vessels were studied. RESULTS: Sildenafil (10(-8) - 3 x 10(-5) mol/L) caused concentration-dependent relaxation in the internal mammary arteries, radial arteries, and forearm veins. In the coronary arteries, sildenafil had a modest relaxant effect. In addition, sildenafil amplified the relaxation induced by sodium nitroprusside in all four vessels. Relaxation was unaffected by the inhibitor of nitric oxide synthase NG-monomethyl-L-arginine (10(-4) mol/L). Compared with zaprinast, sildenafil was eight to ten times more potent in terms of EC50 values. CONCLUSIONS: The direct relaxant effects of sildenafil together with its synergistic interaction with nitric oxide donors should be considered in patients undergoing coronary bypass surgery, patients with low blood pressure, and patients receiving antihypertensive regimes.

Contractile effects of arginine analogues on human internal thoracic and radial arteries.

OBJECTIVES: Plasma levels of endogenous guanidino-substituted analogues of L -arginine are increased in various pathologic conditions. In the present study we determined the effects of some of these compounds on basal and stimulated release of nitric oxide in human internal thoracic and radial arteries. METHODS: Rings of human internal thoracic and radial arteries were obtained from 16 multiorgan donors. The rings were suspended in organ baths for isometric recording of tension. RESULTS: N(G)-monomethyl L -arginine (10(-6) to 10(-3) mol/L) and N(G),N(G)-dimethyl L -arginine (10(-6) to 10(-3) mol/L) caused concentration- and endothelium-dependent contractions. Maximal force of contractions for N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine in the internal thoracic artery were 18.0% +/- 4.3% and 17.8% +/- 3.8%, respectively, of the contraction to 100 mmol/L KCl, and those found in the radial artery were 9.6% +/- 2.5% and 9.1% +/- 2.4%, respectively. Aminoguanidine (10(-5) to 3 x 10(-3) mol/L) and methylguanidine (10(-5) to 3 x 10(-3) mol/L) produced endothelium-independent contractions. L -Arginine (10(-3) mol/L) prevented the contractions by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine but did not change contractions induced by aminoguanidine and methylguanidine. N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine inhibited, in a concentration-dependent manner, the endothelium-dependent relaxation to acetylcholine in the internal thoracic artery and had little attenuating effect in the radial artery; aminoguanidine and methylguanidine were without effect. CONCLUSIONS: The results suggest that the contractions induced by N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine are due to inhibition of both basal and stimulated nitric oxide production, whereas aminoguanidine and methylguanidine do not affect the synthesis of nitric oxide. An increase in the plasma concentration of N(G)-monomethyl L -arginine and N(G),N(G)-dimethyl L -arginine is likely to represent a risk factor for abnormal vasomotor tone in conduit arteries used as coronary grafts.

Identification of a natural soluble form of human CD5.

CD5 is a 67 kDa type I glycoprotein which belongs to the Scavenger Receptor Cysteine-Rich (SRCR) family of receptors. This family includes either cell-surface (e.g. CD6) or secreted (e.g. Spalpha) proteins implicated in the development of the immune system and the regulation of immune responses. In this study, we purified and characterised a circulating natural soluble CD5 form (nsCD5) which is indistinguishable (in apparent molecular mass, glycosylation pattern, and antibody reactivity) from a recombinant soluble CD5 form (rsCD5) composed of the three extracellular SCRC domains. The nsCD5 is a N-glycosylated 52 kDa molecule present in normal human serum and in supernatants of in vitro phorbol ester- and CD3-stimulated peripheral blood mononuclear cells. The nsCD5 concentration in sera from healthy donors is relatively low (median 1.75 ng/ml, rn=166) and is similar to that found in sera from patients suffering of various autoimmune (systemic lupus erythematosus, primary Sjogren syndrome, rheumatoid arthritis) and non-autoimmune (chronic renal failure, B-cell chronic lymphocytic leukemia) disorders. In vitro experiments indicate that nsCD5 is released by proteolytic cleavage of the membrane form. These results represent the first evidence of proteolytic release of a transmembrane SRCR family member following cell activation.

Relevance of individual CD5 extracellular domains on antibody recognition, glycosylation and co-mitogenic signalling.

CD5 is a type I glycoprotein which modulates T- and B-cell receptor-mediated signals and is expressed by thymocytes, mature T cells and a subset of mature B cells. The extracellular region of CD5 is composed of three scavenger receptor cysteine-rich domains (D1, D2, D3) for which only limited functional and structural data are available. Using cell transfectants expressing ectodomain-deficient CD5 molecules or CD5 immunoglobulin fusion proteins, we analysed individual CD5 domains with respect to monoclonal antibody binding specificity, glycosylation, and co-mitogenic signalling. Our results show the presence of N-linked oligosaccharides on D1 and D2, but not on D3. D1, the most amino-terminal domain, is predicted to be the most appropriately placed domain for an interaction with a ligand. This domain is recognised by a large panel of well characterised CD5 mAbs, reflecting its higher immunogenicity. In an attempt to develop mAbs with specificity for the more conserved membrane-proximal domains, we generated a unique mAb, named 83-C4, whose binding mapped to D3. Co-stimulatory studies revealed no significant differences between anti-D1 and anti-D3 mAbs. The high interspecies conservation of D3 implies a conserved role of this domain in CD5 function and the 83-C4 mAb promises to be a valuable tool in exploring this.

Interaction of recombinant and natural soluble CD5 forms with an alternative cell surface ligand.

CD5, a member of the scavenger receptor cysteine-rich (SRCR) receptor family, plays a role in the thymocyte maturation, T cell activation and T cell-antigen-presenting cell interactions. To date only CD5 ligands (CD5L) compatible with a T-B co-stimulatory role have been described (CD72, gp40-80 and IgV(H) framework region) so the existence of alternative CD5L involved in other aspects of T cell biology warrants further exploration. Here we characterize the cell binding properties of a recombinant soluble human CD5 extracellular domain glycoprotein (rsCD5). In contrast to previously characterized ligands, this molecule binds to a broadly distributed cell surface receptor expressed on monocytes, lymphocytes and various cell lines of lymphoid, myelomonocytic and epithelial origin. The cell binding of rsCD5 is divalent cation independent and inhibited by high molar concentrations of certain monosaccharides. Both human CD5 Ig fusion proteins and a natural soluble CD5 form (present in human serum and resulting from proteolytic cleavage following lymphocyte activation) reproduce the cell binding pattern of rsCD5 and block its binding in a competitive form. The involvement of the most N-terminal CD5 SRCR domains (D1 and D2) in binding is deduced from competition cell binding assays with CD5 Ig fusion proteins. These results imply a novel CD5/CD5L interaction model recalling some aspects of the interaction of CD6 with activated leukocyte cell adhesion molecule (ALCAM).

Arginine vasopressin enhances sympathetic constriction through the V1 vasopressin receptor in human saphenous vein.

BACKGROUND: Arginine vasopressin (AVP) not only acts directly on blood vessels through V1 receptor stimulation but also may modulate adrenergic-mediated responses in animal experiments in vivo and in vitro. The aim of the present study was to investigate whether AVP can contribute to an abnormal adrenergic constrictor response of human saphenous veins. METHODS AND RESULTS: Saphenous vein rings were obtained from 32 patients undergoing coronary artery bypass surgery. The vein rings were suspended in organ bath chambers for isometric recording of tension. AVP (3x10[-9] mol/L) enhanced the contractions elicited by electrical field stimulation at 1, 2, and 4 Hz (by 80%, 70%, and 60%, respectively) and produced a leftward shift of the concentration-response curve to norepinephrine (half-maximal effective concentration decreased from 6.87x10[-7] to 1.04x10[-7] mol/L; P<.05). The V1 vasopressin receptor antagonist d(CH2)5Tyr(Me)AVP (10[-6] mol/L) prevented the potentiation evoked by AVP. The selective V1 receptor agonist [Phe,2 Orn8]-vasotocin (3x[-10]-9 mol/L) induced potentiation of electrical stimulation-evoked responses, which was also inhibited in the presence of the V1 receptor antagonist (10[-6] mol/L). In contrast, the V2 receptor agonist desmopressin (10[-9] to 10[-7] mol/L) did not modify neurogenic responses, and the V2 receptor antagonist [d(CH2)5, D-Ile,2 Ile,4 Arg8]-vasopressin (10[-8] to 10[-6] mol/L) did not prevent the potentiation induced by AVP. The dihydropyridine calcium antagonist nifedipine (10[-6] mol/L) did not affect the potentiating effect of AVP. CONCLUSIONS: The results suggest that low concentrations of AVP facilitate sympathetic neurotransmission and potentiate constrictor effects of norepinephrine in human saphenous veins. These effects appear to be mediated by V1 receptor stimulation and are independent of calcium entry through dihydropyridine calcium channels. Thus, AVP may contribute to vascular mechanisms involved in acute ischemic syndromes associated with venous grafts, particularly if the sympathetic nervous system is activated.

Endothelium-dependent relaxation of human saphenous veins in response to vasopressin and desmopressin.

PURPOSE: The goal of this study was to determine the effects of vasopressin and the selective V2-receptor agonist desmopressin on human saphenous veins, with special emphasis on endothelium-mediated responses. METHODS: Human saphenous vein segments were obtained from 35 patients undergoing coronary bypass surgery. Paired segments, one normal and the other deendothelized by gentle rubbing, were mounted for isometric recording of tension in organ baths. Concentration-response curves to vasopressin and desmopressin were determined in the presence and in the absence of either the V1-receptor antagonist d(CH2)5Tyr (Me)AVP (10(-6) mol/L), the V1-V2-receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (10(-6) mol/L), indomethacin (10(-6) mol/L), or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 10(-4) mol/L). RESULTS: In vein rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with a concentration of vasopressin producing half-maximal contractions (EC50) of 3.44 x 10(-8) mol/L. The vasopressin V1-receptor antagonist (10(-6) mol/L) displaced the control curve to vasopressin 9.86-fold to the right in a parallel manner. In precontracted vein rings previously treated with the V1-antagonist (10(-6) mol/L) vasopressin caused endothelium-dependent relaxations. This relaxation was reduced significantly by indomethacin (10(-6) mol/L) and unaffected by the V1-V2-receptor antagonist (10(-6) mol/L) or by L-NAME (10(-4) mol/L). Desmopressin caused endothelium-dependent relaxations in precontracted vein rings that were inhibited by the mixed V1-V2-receptor antagonist and by indomethacin, but not by the V1-antagonist or by pretreatment with L-NAME. CONCLUSIONS: These observations indicate that vasopressin exerts contractile effects on human saphenous vein by V1-receptor stimulation. Vasopressin causes dilatation of human saphenous vein only if V1-receptor blockade is present. This relaxation appears to be mediated by the release of relaxant prostaglandins, probably derived from endothelial cells, and is independent of V2-receptor stimulation or release of nitric oxide. Desmopressin elicits relaxation that is largely dependent on V2-receptor stimulation, which may bring about the release of dilating prostaglandins from the endothelial cells.

Increased responsiveness of human pulmonary arteries in patients with positive bronchodilator response.

1. The effects of noradrenaline, endothelin-1, acetylcholine and sodium nitroprusside were studied in isolated pulmonary arteries obtained from 14 patients undergoing lobectomy for lung carcinoma. Seven patients had shown increased response to a bronchodilator test prior to operation. In the remaining patients (control) the bronchodilator test was negative. 2. Artery rings from patients with a positive bronchodilator response showed greater contraction to noradrenaline (pD2 = 6.44 +/- 0.1; Emax = 93 +/- 9% of response to 100 mM KCl) and endothelin-1 (pD2 = 8.92 +/- 0.1; Emax = 130 +/- 16%) than the rings from control patients (pD2 = 6.04 +/- 0.08; Emax = 56 +/- 8% for noradrenaline; pD2 = 8.29 +/- 0.1; Emax = 78 +/- 10% for endothelin-1). There was no significant difference in the contractile responses to 100 mM KCl between arteries from either group of patients. 3. Arterial rings from patients with a positive bronchodilator test achieved 96 +/- 3% of maximal relaxation in response to acetylcholine, whereas rings from control patients achieved a maximal relaxation of 72 +/- 5%. Rings from both the controls and the patients with a positive bronchodilator test achieved complete relaxation in response to sodium nitroprusside but pD2 values were significantly higher in patients with a positive bronchodilator test. 4. Removal of endothelium or treatment with NG-nitro-L-arginine methyl ester of artery rings from both the control and the patients with a positive bronchodilator test reduced the relaxation to acetylcholine (P < 0.05) but did not modify relaxation to sodium nitroprusside. 5. It is concluded that responsiveness of pulmonary arterial smooth muscle to dilator and constrictor agents is increased in patients showing reversibility of airway constriction. Thus hyperresponsiveness of airway smooth muscle may be associated with a similar phenomenon in the surrounding vascular smooth muscle.

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.

Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries.

The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients). Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but not in endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS. Contractile responses to noradrenaline were similar in arteries with and without endothelium. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide, which inhibits the contractile responses of human pulmonary arteries. Although adrenergic nerves seem to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be noradrenaline.