RESUMO
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.
Assuntos
Algoritmos , Hipocalcemia/sangue , Hipocalcemia/epidemiologia , Hormônio Paratireóideo/sangue , Tireoidectomia/efeitos adversos , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipocalcemia/etiologia , Incidência , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Alta do Paciente , Período Pós-Operatório , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Tireoidectomia/métodos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Nanotechnology has had a significant impact on medicine in recent years, its application being referred to as nanomedicine. Nanoparticles have certain properties with biomedical applications; however, in some situations, they have demonstrated cell toxicity, which has caused concern surrounding their clinical use. In this review, we focus on two aspects: first, we summarize the types of nanoparticles according to their chemical composition and the general characteristics of their use in medicine, and second, we review the applications of nanoparticles in vascular alteration, especially in endothelial dysfunction related to oxidative stress. This condition can lead to a reduction in nitric oxide (NO) bioavailability, consequently affecting vascular tone regulation and endothelial dysfunction, which is the first phase in the development of cardiovascular diseases. Therefore, nanoparticles with antioxidant properties may improve vascular dysfunction associated with hypertension, diabetes mellitus, or atherosclerosis.
Assuntos
Vasos Sanguíneos/patologia , Nanomedicina , Nanopartículas/química , Estresse Oxidativo , Animais , Antioxidantes/metabolismo , HumanosRESUMO
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.
Assuntos
Esterno/cirurgia , Tireoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Bócio/cirurgia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
The CD5 lymphocyte surface glycoprotein is a coreceptor involved in the modulation of antigen-specific receptor-mediated activation and differentiation signals. Although first considered a costimulatory molecule in mature peripheral T cells, recent studies of CD5-/- mice have opened the possibility that CD5 may also mediate inhibitory signals that attenuate TCR/CD3- and BCR-mediated triggering in thymocytes and a subgroup of B cells (B-1a cells), respectively. The ultimate molecular basis for these differential modulatory properties of CD5, depending on the context of lymphocyte subset and differentiation stage, are presently unknown and are an issue of current intensive investigation. Here, we review recent reports, both contradictory and complementary, focused on CD5-mediated molecular intracellular signaling events that could provide the basis for its immunomodulatory properties.
Assuntos
Antígenos CD5/fisiologia , Receptores de Antígenos de Linfócitos B/fisiologia , Receptores de Antígenos de Linfócitos T/fisiologia , Transdução de Sinais , Sistema de Sinalização das MAP Quinases , Proteína Quinase C/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Tirosina Fosfatases/fisiologia , Proteínas Tirosina Quinases/fisiologiaRESUMO
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.
Assuntos
Doenças das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Laparoscopia , Cirurgia Vídeoassistida/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
Assuntos
Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Endotélio Vascular/efeitos dos fármacos , Norepinefrina/farmacologia , Receptores de Tromboxanos/antagonistas & inibidores , Tromboxano A2/análogos & derivados , Tromboxano A2/farmacologia , Vasoconstritores/farmacologia , Idoso , Bloqueadores dos Canais de Cálcio/farmacologia , Di-Hidropiridinas/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Estimulação Elétrica , Endotélio Vascular/metabolismo , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Nifedipino/farmacologia , Cloreto de Potássio/farmacologia , Veia Safena , Estimulação QuímicaRESUMO
The present study was designed to investigate the influence of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human cerebral arteries to electrical field stimulation (EFS) and norepinephrine. Rings of human middle cerebral artery were obtained during autopsy of 19 patients who had died 3-8 h before. EFS (1-8 Hz) induced frequency-dependent contractions that were abolished by tetrodotoxin, prazosin, and guanethidine (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. N(G)-monomethyl L-arginine (L-NMMA 10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but did not influence responses of endothelium-denuded arteries. L-arginine (10(-4) M) reversed the potentiating effects of L-NMMA on EFS-induced contractions. Norepinephrine induced concentration-dependent contractions, which were similar in arteries with and without endothelium or in arteries treated with L-NMMA. Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS or on the inhibition by L-NMMA of acetylcholine-induced relaxation. These results suggest that the contractile response of human cerebral arteries to EFS is modulated by nitric oxide mainly derived from endothelial cells; although adrenergic nerves appear to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be norepinephrine. The effects of L-NMMA in this preparation appear to be due to inhibition of nitric oxide formation rather than caused by cyclooxygenase activation.
Assuntos
Artérias Cerebrais/fisiologia , Endotélio Vascular/metabolismo , Óxido Nítrico/fisiologia , Sistema Nervoso Simpático/fisiologia , Vasoconstrição/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artérias Cerebrais/efeitos dos fármacos , Estimulação Elétrica , Feminino , Humanos , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/antagonistas & inibidores , Norepinefrina/farmacologia , ômega-N-Metilarginina/farmacologiaRESUMO
Endothelin constricted human isolated cerebral arteries in a concentration-dependent manner. The maximal tension developed, as well as EC50 values were similar in arteries with and without endothelium. Removal of extracellular calcium or addition of the calcium antagonist nicardipine (10(-6)M), attenuated but did not abolish responses to endothelin. These experiments show that the endothelin-induced contraction in human cerebral arteries is not linked to the presence of intact endothelial cells. The data also show that the contractile effects of endothelin cannot be explained solely by an action on voltage-dependent calcium channels.
Assuntos
Canais de Cálcio/fisiologia , Endotélio Vascular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Peptídeos/farmacologia , Adulto , Idoso , Artérias Cerebrais/efeitos dos fármacos , Endotelinas , Endotélio Vascular/metabolismo , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Nicardipino/farmacologiaRESUMO
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.
Assuntos
Norepinefrina/metabolismo , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Transmissão Sináptica/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos , Adulto , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Óxido Nítrico/fisiologia , Nitroprussiato/farmacologia , Norepinefrina/farmacologia , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Purinas , Purinonas/farmacologia , Citrato de Sildenafila , SulfonasRESUMO
1. The effects of vasopressin and deamino-8-D-arginine vasopressin (DDAVP, desmopressin) were studied in artery rings (0.8-1 mm in external diameter) obtained from portions of human omentum during the course of abdominal operations (27 patients). 2. In arterial rings under resting tension, vasopressin produced concentration-dependent, endothelium-independent contractions with an EC50 of 0.59 +/- 0.12 nM. The V1 antagonist d(CH2)5Tyr(Me)AVP (1 microM) and the mixed V1-V2 antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (0.01 microM) displaced the control curve to vasopressin to the right in a parallel manner without differences in the maximal responses. In the presence of indomethacin (1 microM) the contractile response to vasopressin was significantly increased (P < 0.01). 3. In precontracted arterial rings, previously treated with the V1 antagonist, d(CH2)5Tyr(Me)AVP (1 microM), vasopressin produced endothelium-dependent relaxation. This relaxation was reduced significantly (P < 0.05) by indomethacin (1 microM) and unaffected by the V1-V2 receptor antagonist desGly-d(CH2)5D-Tyr(Et)ValAVP (1 microM) or by NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM). 4. The selective V2 receptor agonist, DDAVP, caused endothelium-independent, concentration-dependent relaxations in precontracted arterial rings that were inhibited by the mixed V1-V2 receptor antagonist, but not by the V1 receptor antagonist or by pretreatment with indomethacin or L-NAME. 5. Results from this study suggest that vasopressin is primarily a constrictor of human mesenteric arteries by V1 receptor stimulation; vasopressin causes dilatation only during V1 receptor blockade. The relaxation appears to be mediated by the release of vasodilator prostaglandins from the endothelial cell layer and is independent of V2 receptor stimulation or release of nitric oxide. In contrast, the relaxation induced by DDAVP is largely dependent on stimulation of V2 receptors.
Assuntos
Desamino Arginina Vasopressina/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Vasopressinas/farmacologia , Adulto , Arginina/análogos & derivados , Arginina/farmacologia , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Feminino , Humanos , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inibidores , Vasopressinas/antagonistas & inibidoresRESUMO
1. The aim of the present study was to investigate in rat mesenteric artery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10[10]-10[-7] M) caused concentration-dependent contractions (pD2 = 8.36+/-0.09). The V1-receptor antagonist d(CH2)5Tyr(Me)AVP (10[-9]-10[-8] M) produced parallel rightward shifts of the control curve for vasopressin. Schild analysis yielded a pA2 value of 9.83 with a slope of 1.10+/-0.14. 3. Vasopressin (3 x 10[-10] and 10[-9] M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms duration for 30 s) and produced leftward shifts of the concentration-response curve for noradrenaline. The V1-receptor antagonist induced concentration-dependent inhibitions of potentiation induced by vasopressin. The selective V1-receptor agonist [Phe2, Orn8]-vasotocin (3 x 10[10] and 10[-9] M) induced potentiation of electrical stimulation-evoked responses which was also inhibited in the presence of the V1 antagonist (10[-8] M). In contrast, the V2-receptor agonist deamino-8-D-arginine vasopressin (desmopressin 10[-8]-10[-7] M) did not modify the electrical stimulation-induced responses and the V2-receptor antagonist [d(CH2)5, D-Ile2, Ile4, Arg8]-vasopressin (10[-8]-10[-7] M) did not affect the potentiation evoked by vasopressin. 4. In artery rings contracted by 10(-6) M noradrenaline in the presence of 10(-6) M guanethidine and 10(-6) M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10(-9) M vasopressin but abolished by 10(-6) M tetrodotoxin. 5. Vasopressin also potentiated contractions elicited by KCl and contractions induced by addition of CaCl2 to KCl depolarized vessels. The augmenting effects were inhibited by the V1 antagonist. 6. In the presence of the calcium antagonist nifedipine (10[-6] M), vasopressin failed to enhance the contractile responses to electrical stimulation, noradrenaline and KCl. 7. The results demonstrate that low concentrations of vasopressin strongly potentiate the contractions to adrenergic stimulation and KCl depolarization. This effect appears to be mediated by V1 receptor stimulation which brings about an increase in calcium entry through dihydropyridine-sensitive calcium channels.
Assuntos
Artérias Mesentéricas/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Receptores Adrenérgicos/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos , Vasopressinas/farmacologia , Animais , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cocaína/farmacologia , Estimulação Elétrica , Antagonistas de Hormônios/farmacologia , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Nifedipino/farmacologia , Norepinefrina/farmacologia , Cloreto de Potássio/farmacologia , Ratos , Ratos Wistar , Vasotocina/análogos & derivados , Vasotocina/farmacologiaRESUMO
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.
Assuntos
Hiper-Reatividade Brônquica/fisiopatologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Idoso , Broncodilatadores , Endotélio/fisiologia , Inibidores Enzimáticos/farmacologia , Humanos , Técnicas In Vitro , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
1. The aim of the present study was to characterize neurogenic and pharmacological responses of human penile deep dorsal vein and to determine whether the responses are mediated by nitric oxide from neural or endothelial origin. 2. Ring segments of human penile deep dorsal vein were obtained from 22 multiorgan donors during procurement of organs for transplantation. The rings were suspended in organ bath chambers for isometric recording of tension. We then studied the contractile and relaxant responses to electrical field stimulation and to vasoactive agents. 3. Electrical field stimulation (0.5-2 Hz) and noradrenaline (3 x 10(-10)-3 x 10(-5) M) caused frequency- and concentration-dependent contractions that were of greater magnitude in veins denuded of endothelium. The inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, l0(-4) M) increased the adrenergic responses only in rings with endothelium. 4. In preparations contracted with noradrenaline in the presence of guanethidine (10(-6) M) and atropine (10(-6) M), electrical stimulation induced frequency-dependent relaxations. This neurogenic relaxation was prevented by L-NAME, methylene blue (3 x 10(-5) M) and tetrodotoxin (10(-6) M), but was unaffected by removal of endothelium. 5. Acetylcholine (10(-8)-3 x 10(-5) M) and substance P (3 x 10(-11) -3 x 10(-7) M) induced endothelium-dependent relaxations. In contrast, sodium nitroprusside (10(-9)-3 x 10(-5) M) and papaverine (10(-8) 3 x 10(-5) M) caused endothelium-independent relaxations. 6. The results provide functional evidence that the human penile deep dorsal vein is an active component of the penile vascular resistance through the release of nitric oxide from both neural and endothelial origin. Dysfunction in any of these sources of nitric oxide should be considered in some forms of impotence.
Assuntos
Músculo Liso Vascular/inervação , Músculo Liso Vascular/fisiologia , Pênis/irrigação sanguínea , Acetilcolina/farmacologia , Adolescente , Adulto , Idoso , Estimulação Elétrica , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiologia , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/metabolismo , Nitroprussiato/farmacologia , Norepinefrina/farmacologia , Papaverina/farmacologia , Substância P/farmacologia , Vasoconstritores/farmacologia , Vasodilatadores/farmacologia , Veias/efeitos dos fármacos , Veias/inervação , Veias/fisiologiaRESUMO
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.
Assuntos
Guanidinas/farmacologia , Óxido Nítrico/metabolismo , Artéria Radial/efeitos dos fármacos , Artérias Torácicas/efeitos dos fármacos , Vasoconstritores/farmacologia , Adolescente , Adulto , Análise de Variância , Arginina/análogos & derivados , Arginina/farmacologia , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Artéria Radial/metabolismo , Análise de Regressão , Artérias Torácicas/metabolismoRESUMO
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.
Assuntos
Arginina/análogos & derivados , Arginina/sangue , Óxido Nítrico/antagonistas & inibidores , Artéria Renal/metabolismo , Acetilcolina/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
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.
Assuntos
Desamino Arginina Vasopressina/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Receptores de Vasopressinas/fisiologia , Fármacos Renais/farmacologia , Artéria Renal/fisiologia , Vasodilatação/efeitos dos fármacos , Adulto , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Técnicas In Vitro , Indometacina/farmacologia , Contração Isométrica , Masculino , Pessoa de Meia-Idade , Músculo Liso Vascular/efeitos dos fármacos , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Prostaglandinas/metabolismo , Artéria Renal/citologia , Artéria Renal/efeitos dos fármacosRESUMO
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.
Assuntos
3',5'-GMP Cíclico Fosfodiesterases/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Piperazinas/farmacologia , Purinonas/farmacologia , Vasodilatação/efeitos dos fármacos , Vasos Coronários/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Artéria Torácica Interna/efeitos dos fármacos , Purinas , Artéria Radial/efeitos dos fármacos , Citrato de Sildenafila , Sulfonas , Veias/efeitos dos fármacosRESUMO
The present study was designed to investigate the influence of endothelium-derived nitric oxide on the contractile responses of isolated human omental arteries to electrical field stimulation and noradrenaline. We measured isometric tension in artery rings obtained from portions of human omentum during the course of abdominal operations (32 patients). Electrical field stimulation induced frequency-dependent contractions which were abolished by tetrodotoxin (10(-6) M) and prazosin (10(-6) M), thus indicating that this effect was due to noradrenaline released from adrenergic nerves acting on alpha 1-adrenoceptors. The increases in tension induced by electrical field stimulation were of greater magnitude in arteries denuded of endothelium. NG-Nitro-L-arginine (L-NAME, 10(-4) M) potentiated the contractile response to electrical field stimulation in artery rings with endothelium but did not influence the contractile responses of 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). Contractile responses to noradrenaline were similar in arteries with and without endothelium. L-NAME (10(-4) M) had no significant effect on the contractile responses to noradrenaline. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide which inhibits the contractile responses of human omental arteries. The constrictor responses to noradrenaline are not modulated by the endothelium.
Assuntos
Artérias/efeitos dos fármacos , Endotélio Vascular/fisiologia , Músculo Liso Vascular/efeitos dos fármacos , Óxido Nítrico/fisiologia , Norepinefrina/farmacologia , Vasoconstrição/efeitos dos fármacos , Adulto , Idoso , Arginina/análogos & derivados , Arginina/farmacologia , Artérias/fisiologia , Estimulação Elétrica , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Técnicas In Vitro , Indometacina/farmacologia , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , NG-Nitroarginina Metil Éster , Óxido Nítrico/antagonistas & inibidores , Omento/irrigação sanguínea , Estereoisomerismo , Tetrodotoxina/farmacologiaRESUMO
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.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Músculo Liso/fisiologia , Receptores de Vasopressinas/fisiologia , Transmissão Sináptica/fisiologia , Adulto , Antagonistas dos Receptores de Hormônios Antidiuréticos , Arginina Vasopressina/análogos & derivados , Arginina Vasopressina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Estimulação Elétrica , Antagonistas de Hormônios/farmacologia , Humanos , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Nifedipino/farmacologia , Norepinefrina , Cloreto de Potássio , Receptores de Vasopressinas/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Ducto Deferente/efeitos dos fármacos , Ducto Deferente/metabolismo , Vasoconstritores/farmacologia , Vasopressinas/farmacologiaRESUMO
To examine whether low concentrations of endothelin-1 potentiate the vasoconstrictor response to adrenergic stimulation, we recorded the isometric response of rings of rabbit pulmonary artery to electrical stimulation and noradrenaline. Endothelin-1 (10(-10) M) potentiated the contractions induced by electrical stimulation and noradrenaline. The endothelin ET(B) receptor antagonist (2,6-dimethylpiperidinecarbonyl-gamma-methyl-Leu-N(in)-[Methoxycarbonyl]-D-Trp-D-Nle) (BQ-788, 10(-6) M), but not the endothelin ET(A) receptor antagonist cyclo(D-Asp-Pro-D-Val-Leu-D-TRP) (BQ-123, 10(-6) M), inhibited the potentiating effects of endothelin-1. Pretreatment with the cyclooxygenase inhibitor indomethacin, the thromboxane synthase inhibitor furegrelate and the thromboxane receptor antagonist [1S-[1alpha,2alpha(Z),3alpha,4alpha]]-7-[3-[[[[(1-oxoheptyl)amino]acetyl]amino] methyl]-7-oxabicyclo-[2.2.1]hept-2-yl]-5-heptenoic acid (SQ-30741) (all at 10(-5) M) prevented the potentiation induced by endothelin-1 on adrenergic stimulation. The Ca(2+) channel antagonist nifedipine (10(-6) M) did not affect the potentiation induced by endothelin-1. The results indicate that endothelin-1 potentiates the responses to electrical stimulation and noradrenaline by activating endothelin ET(B) receptors. This potentiation depends on the production of cyclooxygenase-generated factors, probably thromboxane A(2).