RESUMO
BACKGROUND: We developed an automated, chat-based, digital health intervention using Bluetooth-enabled home spirometers to monitor for complications of lung transplantation in a real-world application. METHODS: A chat-based application prompted patients to perform home spirometry, enter their forced expiratory volume in 1 second (FEV1), answer symptom queries, and provided patient education. The program alerted patients and providers to substantial FEV1 decreases and concerning symptoms. Data was integrated into the electronic health record (EHR) system and dashboards were developed for program monitoring. RESULT: Between May 2020 and December 2021, 544 patients were invited to enroll, of whom 427 were invited remotely and 117 were enrolled in-person. 371 (68%) participated by submitting ≥1 FEV1 values. Overall engagement was high, with an average of 197 unique patients submitting FEV1 data per month. In-person enrollees submitted an average of 4.6 FEV1 values per month and responded to 55% of scheduled chats. Home and laboratory FEV1 values correlated closely (rho = 0.93). There was an average of 133 ± 59 FEV1 decline alerts and 59 ± 23 symptom alerts per month. 72% of patients accessed education modules, and the program had a high net promoter score (53) amongst users. CONCLUSIONS: We demonstrate that a novel, automated, chat-based, and EHR-integrated home spirometry intervention is well accepted, generates reliable assessments of graft function, and can deliver automated feedback and education resulting in moderately-high adherence rates. We found that in-person onboarding yields better engagement and adherence. Future work will aim to demonstrate the impact of remote care monitoring on early detection of lung transplant complications.
Assuntos
Pneumopatias , Transplante de Pulmão , Humanos , Espirometria/métodos , Volume Expiratório Forçado , Testes de Função RespiratóriaRESUMO
AIM: Contrast-induced nephropathy (CIN) is most commonly defined as acute renal failure occurring within 48-72 h of exposure to intravascular radiographic contrast medium that is not attributable to other causes. In international literature a 25% increase in serum creatinine levels or an increase in absolute values of 0.5 mg/dL from baseline has been suggested to define CIN. The reported incidence of CIN varies widely, ranging from 2% to 50%. This variability results from differences in the presence or absence of risk factors. With a retrospective analysis authors evaluated the use of NaCl saline hydration and N-acetyl cysteine (NAC) to prevent CIN in different populations of patients at high and low risk undergoing coronary artery angiography. METHODS: From January 2007 to December 2008, 597 patients underwent coronary artery angiography with a low osmolarity contrast agent. Nephrotoxic drugs such as diuretics, metformin, ACE-I and ARBs were stopped at least 24 h before the procedure. The population was divided into two groups: group A (high risk 342 patients, 57.2%) identified for the presence of at least one risk factor such as diabetes, age >65 years, baseline creatinine >1.4 mg/dL and group B (low risk 255 patients, 42.8%) for the absence of any of the risk mentioned above. Only group A was treated with a saline hydration (1 mL/kg/h) plus NAC 600 mg 12 h before and 12 h after the procedure. RESULTS: The overall incidence of CIN was 6.7% (40 patients). In particular, the incidence of CIN was 4.4% (15 patients) in the group A and 9.8% (25 patients) in the group B respectively (P=0.017). Interestingly, the Contrast Index (volume administrated/theoretical maximum volume) was significantly lower in group B (P<0.005). In the multivariate analysis, including risk factors such as age, diabetes, hypertension, hypercholesterol-mia, current smoke, baseline creatinine level, Contrast Index and hydration, the last variable was the only one inversely correlated independently with the incidence of CIN (P=0.001). CONCLUSIONS: The hydration with saline and NAC is an effective and low-cost tool in preventing CIN in patients undergoing coronary artery angiography and, according to the current guidelines, should be used in all high-risk patients. Present results show that even in patients at low risk for CIN, hydration could be useful: in fact, despite the Contrast Index was significantly lower in this population, the incidence of CIN was greater, thus suggesting a potential role for hydration also in the low-risk population.
Assuntos
Acetilcisteína/uso terapêutico , Meios de Contraste/efeitos adversos , Angiografia Coronária , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Cloreto de Sódio/uso terapêutico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: Many evidences show that the hormone relaxin plays a pivotal role in the physiology and pathology of the cardiovascular system. This pleiotropic hormone exerts regulatory functions through specific receptors in cardiovascular tissues: in experimental animal models it was shown to induce coronary vasodilation, prevent cardiac damage induced by ischemia/reperfusion and revert cardiac hypertrophy and fibrosis. A tight relationship between this hormone and important metabolic pathways has been suggested, but it is at present unknown if relaxin could regulate cardiac metabolism. Our aim was to study the possible effects of relaxin on cardiomyocyte metabolism. METHODS: Neonatal rat cardiomyocytes were treated with relaxin and (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays (MTT) were performed to assess metabolic activity; while 2-deoxy-D-[3H] glucose and BODIPY-labelled fatty acid incorporations were analyzed to measure glucose and fatty acid uptakes, and western blot was utilized to study the intracellular signaling pathways activated by the hormone. RESULTS: We observed that relaxin at 10 ng/ml was able to increase the level of metabolic activity of cultured neonatal rat cardiomyocytes; the rate of 2-deoxy-D-[3H]glucose incorporation demonstrated that relaxin also induced an increase in glucose uptake. First evidence is also offered that relaxin can activate the master energy sensor and regulator AMPK in cardiomyocytes. Moreover, the treatment of cardiomyocytes with relaxin also induced dose-dependent increases in ERK1/2, AKT, and AS160 phosphorylation. That raise in AS160 phosphorylation induced by relaxin was prevented by the pretreatment with AMPK and AKT pathways inhibitors, indicating that both molecules play important roles in the relaxin effects reported. CONCLUSION: Relaxin can regulate cardiomyocyte metabolism and activate AMPK, the central sensor of energy status that maintains cellular energy homeostasis, and also ERK and AKT, two molecular sensing nodes that coordinate dynamic responses of the cell's metabolic responses.
Assuntos
Adenilato Quinase/metabolismo , Glucose/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relaxina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Transporte Biológico , Metabolismo Energético/efeitos dos fármacos , Masculino , Miócitos Cardíacos/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The results of the current study demonstrate that relaxin inhibits histamine release by mast cells. This effect is related to the peptide concentrations, and could be observed in both isolated rat serosal mast cells stimulated with compound 48/80 or calcium ionophore A 23187, and in serosal mast cells isolated from sensitized guinea pigs and challenged with the antigen. The morphological findings agree with the functional data, revealing that relaxin attenuates calcium ionophore-induced granule exocytosis by isolated rat serosal mast cells. Similar effects of relaxin have also been recognized in vivo by light microscopic and densitometric analysis of the mesenteric mast cells of rats which received the hormone intraperitoneally 20 min before local treatment of the mesentery with calcium ionophore. Moreover, evidence is provided that relaxin stimulates endogenous production of nitric oxide and attenuates the rise of intracellular Ca2+ concentration induced by calcium ionophore. The experiments with drugs capable of influencing nitric oxide production also provide indirect evidence that the inhibiting effect of relaxin on mast cell histamine release is related to an increased generation of nitric oxide. It is suggested that relaxin may have a physiological role in modulating mast cell function through the L-arginine-nitric oxide pathway.
Assuntos
Mastócitos/efeitos dos fármacos , Relaxina/farmacologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Calcimicina/farmacologia , Cálcio/metabolismo , Cobaias , Liberação de Histamina/efeitos dos fármacos , Técnicas In Vitro , Masculino , Mastócitos/metabolismo , NG-Nitroarginina Metil Éster , Óxido Nítrico/biossíntese , Ratos , Ratos WistarRESUMO
Recently, we demonstrated that relaxin (RLX), a peptide hormone of ovarian origin, inhibits growth and promotes differentiation of MCF-7 breast adenocarcinoma cells. We also showed that RLX stimulates the production of nitric oxide (NO) in several cell types. NO has been reported to have antitumor activity by inhibiting proliferation, promoting differentiation, and reducing the metastatic spread of some tumor cell types. In this study, we aimed at evaluating whether RLX influences the L-arginine-NO pathway in MCF-7 cells. The cells were grown in the absence or presence of RLX at different concentrations, and cell proliferation, constitutive and inducible NO synthase activities, nitrite production, and intracellular levels of cyclic GMP were investigated. The results obtained indicate that RLX increases inducible NO synthase activity and potentiates NO production. This was accompanied by an elevation of intracellular cyclic GMP, which is known to mediate the cell response to NO. The RLX-induced activation of the L-arginine-NO pathway in the MCF-7 cells was inversely related to the rate of cell proliferation. These results suggest that the cytostatic effect of RLX on MCF-7 breast cancer cells may rely on its ability to stimulate endogenous production of NO.
Assuntos
Arginina/fisiologia , Neoplasias da Mama/metabolismo , Óxido Nítrico/fisiologia , Relaxina/farmacologia , Neoplasias da Mama/patologia , GMP Cíclico/análise , Feminino , Humanos , Óxido Nítrico Sintase/metabolismo , Timidina/metabolismo , Células Tumorais CultivadasRESUMO
In previous studies, the peptide hormone relaxin (RLX) was found to inhibit mast cell secretion and platelet activation. It has been established that the release of mediators from these cells plays a central pathogenic role in allergic asthma. This prompted us to ascertain whether RLX may counteract the respiratory and histopathological abnormalities of the asthma-like reaction to inhaled antigen in sensitized guinea pigs. Guinea pigs were sensitized with ovalbumin and challenged with the same antigen given by aerosol. Some animals received RLX (30 microg/kg BW, twice daily for 4 days) before antigen challenge. Other animals received inactivated RLX in place of authentic RLX. Respiratory abnormalities, such as cough and dyspnea, were analyzed as were light and electron microscopic features of lung specimens. RLX was shown to reduce the severity of respiratory abnormalities, as well as histological alterations, mast cell degranulation, and leukocyte infiltration in sensitized guinea pigs exposed to ovalbumin aerosol. RLX was also found to promote dilation of alveolar blood capillaries and to reduce the thickness of the air-blood barrier. This study provides evidence for an antiasthmatic property of RLX and raises the possibility of new therapeutic strategies for allergic asthma in humans.
Assuntos
Antígenos/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Ovalbumina/imunologia , Relaxina/uso terapêutico , Administração por Inalação , Animais , Antígenos/administração & dosagem , Asma/fisiopatologia , Brônquios/patologia , Tosse , Dispneia , Cobaias , Pulmão/patologia , Masculino , Ovalbumina/administração & dosagem , Relaxina/administração & dosagem , RespiraçãoRESUMO
Relaxin was previously shown to cause coronary vasodilation and to inhibit mast cell activation through a stimulation of endogenous nitric oxide production. This suggests that relaxin may have beneficial effects on ischemia-reperfusion-induced myocardial injury, which is triggered by endothelial damage and impaired nitric oxide generation. In this study, we tested the effect of relaxin on isolated and perfused guinea pig hearts subjected to ischemia and reperfusion. Ischemia was induced by ligature of the left anterior descending coronary artery; removal of the ligature induced reperfusion. Relaxin, at the concentration of 30 ng/ml of perfusion fluid, causes: a significant increase in coronary flow and in nitric oxide generation; a significant decrease in malonyldialdehyde production and in calcium overload, both markers of myocardial injury; an inhibition of mast cell granule exocytosis and histamine release, which are known to contribute to myocardial damage; a reduction of ultrastructural abnormalities of myocardial cells; an improvement of heart contractility. The beneficial effects of relaxin were blunted by the NO synthase inhibitor L-NMMA. The current study provides first experimental evidence that relaxin has a powerful protective effect on the heart undergoing ischemia and reperfusion acting through a nitric oxide-driven mechanism.
Assuntos
Coração/efeitos dos fármacos , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Óxido Nítrico/fisiologia , Relaxina/farmacologia , Animais , Cálcio/metabolismo , Circulação Coronária/efeitos dos fármacos , Grânulos Citoplasmáticos/ultraestrutura , Inibidores Enzimáticos/farmacologia , Cobaias , Liberação de Histamina/efeitos dos fármacos , Técnicas In Vitro , Masculino , Malondialdeído/antagonistas & inibidores , Mastócitos/efeitos dos fármacos , Mastócitos/ultraestrutura , Contração Miocárdica/efeitos dos fármacos , ômega-N-Metilarginina/farmacologiaRESUMO
The uterus is a site of nitric oxide (NO) production and expresses NO synthases (NOS), which are up-regulated during pregnancy. NO induces uterine quiescence, which is deemed necessary for the maintenance of pregnancy. Relaxin is known to promote uterine quiescence. Relaxin has also been shown to stimulate NO production in several targets. In this study we investigated the effects of relaxin on the NO biosynthetic pathway of the mouse uterus. Estrogenized mice were treated with relaxin (2 microg) for 18 h, and the uterine horns were used for determination of immunoreactive endothelial-type NOS and inducible NOS. Moreover, uterine strips from estrogenized mice were placed in an organ bath, and the effect of relaxin on K+-induced contracture was evaluated in the presence or absence of the NOS inhibitor nitro-L-arginine. Relaxin increases the expression of endothelial-type NOS in surface epithelium, glands, endometrial stromal cells, and myometrium, leaving inducible NOS expression unaffected. Moreover, relaxin inhibits myometrial contractility, and this effect is blunted by nitro-L-arginine, thus indicating that the L-arginine-NO pathway is involved in the relaxant action of relaxin on the myometrium. Because relaxin is elevated during pregnancy, it is suggested that relaxin has a physiological role in the up-regulation of uterine NO biosynthesis during pregnancy.
Assuntos
Óxido Nítrico/biossíntese , Relaxina/fisiologia , Contração Uterina/fisiologia , Útero/metabolismo , Animais , Feminino , Técnicas In Vitro , Camundongos , Óxido Nítrico Sintase/metabolismo , Potássio/farmacologia , Relaxina/farmacologia , Contração Uterina/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/enzimologiaRESUMO
Prolactin (PRL) and Relaxin (RXL) are present in human decidua at term. In previous experiments we observed that the inhibition of spontaneous uterine contractions produced by decidual RLX was masked or absent if the samples were contaminated with PRL. The present study reports the effect of purified human PRL and of sera from hyperprolactinemic patients on the motility of the uterus in vitro. Also, we studied the effect of RLX on the uterus after exposure to PRL. High-PRL sera and purified human PRL produced prompt increases in the frequency and the amplitude of the spontaneous contractions of the rat uterus. PRL antagonized RLX both when the uterus was exposed first to RLX and then to PRL and when it was exposed first to PRL and then to RLX.
Assuntos
Prolactina/farmacologia , Relaxina/farmacologia , Contração Uterina/efeitos dos fármacos , Animais , Bioensaio , Antagonismo de Drogas , Estradiol/análogos & derivados , Estradiol/farmacologia , Feminino , Humanos , Prolactina/sangue , Ratos , Albumina Sérica/farmacologia , Útero/efeitos dos fármacosRESUMO
The production of protein hormones by human placenta, amnion, chorion, and decidua capsularis was studied in in vitro experiments to establish whether the decidua could be considered a specialized structure for the release of PRL. The tissues were incubated in the incubation medium, we found a highly significant rise of PRL during culture of the decidua, while no increase was noticed during culture of the placenta or amnion. Conversely, chorionic somatomammotropin and CG increased greatly and quickly during culture of placenta but not during culture of other tissues. No significant change was found in GH. The total PRL released into the medium from decidua was 3 times higher than the initial PRL content of this sittue; addition of puromycin to the incubation medium reduced both the tissue content and the release of PRL to almost 50% of the control values. This result raises the possibility of a specific endocrine activity of decidua capsularis. The PRL-secreint cells of the decidua probably do not possess dopamine receptors, since bromocriptine, when added to the medium, did not influence the release of PRL, confirming our previous in vivo observations.
Assuntos
Decídua/fisiologia , Prolactina/biossíntese , Âmnio/metabolismo , Bromocriptina/farmacologia , Córion/metabolismo , Decídua/efeitos dos fármacos , Feminino , Humanos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Gravidez , Puromicina/farmacologiaRESUMO
To investigate the possible role of PRL in the control of fetal adrenal function, blood samples were collected from maternal peripheral and cord blood from six women at delivery, who had received treatment with bromocriptine (3.75--35 mg daily) for the entire gestation. A group of eight untreated parturients served as control. Parameters measured were PRL and dehydroepiandrosterone, the latter as an indicator of fetal adrenal function. PRL was significantly suppressed (P < 0.002), whereas dehydroepiandrosterone was not influenced by bromocriptine treatment. The results indicate that the control of fetal production of androgenic substrate by the adrenals is not specifically PRL dependent.
Assuntos
Glândulas Suprarrenais/embriologia , Desidroepiandrosterona/sangue , Gravidez , Prolactina/sangue , Glândulas Suprarrenais/fisiologia , Adulto , Bromocriptina/uso terapêutico , Feminino , Sangue Fetal/metabolismo , Humanos , Troca Materno-FetalRESUMO
Relaxin (RLX) has been purified from the ovary of the pregnant pig and rat but not from human tissues. Our study shows that tissue extracts and incubation media of in vitro culture of human decidua contain a substance with relaxin bioactivities: the inhibition of spontaneous uterine contractions and the elongation of the interpubic ligament. After chromatography on Sephadex G-50 the bioactivity was retained in a protein fraction of approximately 6000 daltons mol wt. The yield of RLX from decidua was 15--33.5 GPU/g fresh tissue. This opens the possibility of the isolation and purification of RLX in the human species.
Assuntos
Decídua/análise , Relaxina/análise , Animais , Bioensaio , Técnicas de Cultura , Feminino , Cobaias , Humanos , Camundongos , Gravidez , Sínfise Pubiana/efeitos dos fármacos , Ratos , Relaxina/farmacologia , Suínos , Contração Uterina/efeitos dos fármacosRESUMO
The peptide hormone relaxin (RLX) has been shown to elicit a powerful vasodilatory response in several target organs. This response is mediated by the stimulation of intrinsic nitric oxide (NO) generation. The present study was designed to clarify whether RLX directly promotes the relaxation of vascular smooth muscle cells through stimulation of NO generation. Vascular smooth muscle cells from bovine aortas were incubated with RLX at concentrations ranging from 1 nmol/L to 1 micromol/L. The expression and activity of NO synthase, production of NO, and the intracellular levels of cGMP and Ca2+ were determined. The cell morphology and signal transduction mechanisms of these bovine aortic smooth muscle cells in response to RLX were also studied. RLX stimulated the expression of immunoreactive inducible NO synthase and increased significantly and in a concentration-related fashion inducible NO synthase activity, NO generation, and intracellular cGMP levels. Concurrently, RLX significantly decreased cytosolic Ca2+ concentrations and caused changes in cell shape and the actin cytoskeleton that were consistent with cell relaxation. The signal transduction mechanisms leading to the enhanced expression of inducible NO synthase protein and activity caused by RLX involve the activation of tyrosine kinase, phosphatidylcholine-phospholipase C, and the transcription factor nuclear factor-kappaB, similar to bacterial endotoxins and proinflammatory cytokines. This study suggests that RLX is an endogenous agent capable of regulating vascular tone by activation of the L-arginine-NO pathway in vascular smooth muscle cells.
Assuntos
Arginina/metabolismo , Músculo Liso Vascular/fisiologia , Óxido Nítrico/metabolismo , Relaxina/fisiologia , Análise de Variância , Animais , Arginina/fisiologia , Cálcio/metabolismo , Bovinos , Células Cultivadas , Ativação Enzimática , Guanosina Monofosfato/metabolismo , Imuno-Histoquímica , Microscopia Eletrônica , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Fosfatidilcolinas/metabolismo , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Fosfolipases Tipo C/metabolismoRESUMO
An unexpected 20-week-old pregnancy was found in a young acromegalic who had been treated with 10 mg bromocriptine/day for 10 months. The drug was continued throughout the period of gestation. No growth of the pituitary adenoma was noticed. The intrauterine development of the fetus was normal. Bromocriptine therapy had no discernible effect on the expected patterns of secretion of placental hormones, but inhibited completely the increase of PRL in the serum of the mother. Maternal plasma GH concentrations were very high in spite of the treatment and progressively declined after delivery. The plasma GH level was normal in the child, but PRL was very low at birth and increased in the following days. The expected high PRL concentration was found in the amniotic fluid. This case study suggests that bromocriptine crosses the human placenta and affects the fetal pituitary, maternal GH does not influence fetal or amniotic GH, and amniotic fluid PRL correlates poorly with either maternal or fetal blood levels and is not affected by bromocriptine.
Assuntos
Acromegalia/sangue , Líquido Amniótico/metabolismo , Bromocriptina/uso terapêutico , Hormônio do Crescimento/metabolismo , Complicações na Gravidez/sangue , Prolactina/metabolismo , Acromegalia/complicações , Acromegalia/tratamento farmacológico , Adulto , Criança , Feminino , Sangue Fetal/metabolismo , Hormônio do Crescimento/sangue , Humanos , Recém-Nascido , Troca Materno-Fetal , Gravidez , Prolactina/sangueRESUMO
OBJECTIVE: In previous studies severe, acute hypertension damaged the endothelium in proximal coronary arteries and selectively potentiated constriction of the artery to serotonin. In the present study we investigated the role of several mechanical factors and of oxygen radicals in this response. DESIGN: To test the role of mechanical factors in the response to acute hypertension, the effect of different magnitudes of elevation of perfusion pressure and the rate of the rise in perfusion pressure were studied. Pharmacologically induced increases in blood pressure were produced by infusion of angiotensin II or phenylephrine. The role of oxygen radicals was tested by measuring responses to serotonin before and after increases in perfusion pressure in dogs treated with a combination of superoxide dismutase and catalase or with deferoxamine. METHODS: In open-chest anesthetized dogs the diameter of the left anterior descending coronary artery (LADCA) was measured using sonomicrometer crystals, and the LADCA was perfused at a constant pressure of 80 mmHg from a reservoir. Responses to serotonin were measured at this perfusion pressure before and after an abrupt increase in perfusion pressure. RESULTS: Intracoronary serotonin (5 or 50 micrograms/min) produced a dose-dependent constriction of the LADCA while increasing coronary flow. Abruptly increasing the coronary perfusion pressure from 80 to 120, 150 or 200 mmHg augmented the constriction to serotonin twofold, whereas increases in perfusion pressure to 100 mmHg had no effect. Increasing coronary pressure slowly (over a 4-min period) from 80 to 200 mmHg augmented constriction to serotonin. Inducing acute hypertension (coronary pressure 200 mmHg) pharmacologically with angiotensin II also augmented constriction to serotonin, whereas phenylephrine-induced hypertension did not. Superoxide dismutase, a scavenger of superoxide anions and catalase, a scavenger of hydrogen peroxide, prevented the augmented constriction to serotonin following a pressure increase. Deferoxamine, which prevents generation of hydroxyl radicals from superoxide anions and hydrogen peroxide, also prevented the enhanced constriction to serotonin following an acute pressure increase. CONCLUSIONS: Moderate physiological increases in pressure, induced either mechanically or pharmacologically, can augment the responses to serotonin. Oxygen-derived free radicals, particularly hydroxyl radicals, might be involved in the abnormal response to serotonin following an abrupt increase in coronary pressure.
Assuntos
Circulação Coronária/fisiologia , Hipertensão/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Angiotensina II/farmacologia , Animais , Fenômenos Biomecânicos , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Catalase/farmacologia , Circulação Coronária/efeitos dos fármacos , Desferroxamina/farmacologia , Cães , Sinergismo Farmacológico , Feminino , Radicais Livres , Hipertensão/metabolismo , Masculino , Fenilefrina/farmacologia , Serotonina/farmacologia , Superóxido Dismutase/farmacologia , Vasoconstrição/efeitos dos fármacos , Vasoconstrição/fisiologiaRESUMO
Left ventricular (LV) diastolic function is often impaired in coronary artery disease (CAD). To assess whether verapamil could improve LV diastolic properties, 12 patients with CAD undergoing right- and left-sided cardiac catheterization, as well as simultaneous radionuclide angiography, were studied before and during intravenous administration of verapamil (0.1 mg/kg as a bolus followed by 0.007 mg/kg/min). The heart rate was kept constant by atrial pacing in both studies. LV pressure-volume relations were obtained. Verapamil decreased LV systolic pressure (130 +/- 22 to 117 +/- 16 mm Hg, p less than 0.01) and the end-systolic pressure/volume ratio (2.4 +/- 1.3 to 1.6 +/- 0.5 mm Hg/ml, p less than 0.05), and increased LV end-diastolic (13 +/- 4 to 16 +/- 4 mm Hg, p less than 0.02) and pulmonary capillary pressures (10 +/- 5 to 12 +/- 5 mm Hg, p less than 0.005). Despite such negative inotropic effects, cardiac index increased (3.4 +/- 0.7 to 3.9 +/- 0.6 liters/min/m2, p less than 0.02). The time constant of isovolumic relaxation shortened (63 +/- 14 to 47 +/- 9 ms, p less than 0.02); peak filling rate increased (370 +/- 155 to 519 +/- 184 ml/s, p less than 0.001; 2.6 +/- 1.1 to 3.3 +/- 0.9 end-diastolic counts/s, p less than 0.02; and 4.1 +/- 1.6 to 5.5 +/- 1.5 stroke counts/s, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Angina Pectoris/fisiopatologia , Função Ventricular Esquerda/efeitos dos fármacos , Verapamil/administração & dosagem , Adulto , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/tratamento farmacológico , Cateterismo Cardíaco , Angiografia Coronária , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Pressão Propulsora Pulmonar/efeitos dos fármacos , Verapamil/uso terapêuticoRESUMO
1. Relaxin (RLX) is a multifunctional hormone which, besides its role in pregnancy and parturition, has also been shown to influence the cardiovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid at a concentration of 5 x 10(-9) M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10(-9) M, 5 x 10(-8) M dissolved in 1 ml of perfusion fluid. 2. RLX, given either for a 20-min perfusion or as a bolus in the aortic cannula to guinea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolism, that appeared in the perfusates in a concentration-dependent fashion. 3. The increase in coronary flow and in nitrite in the perfusates induced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA, 10(-4) M). 4. The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dependent vasodilator agent, acetylcholine (ACh, 10(-8)-10(-7) M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, 10(-7)-10(-6) M). The results obtained show that RLX is more effective than ACh and SNP in increasing coronary flow. 5 The results of this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel agent capable of improving myocardial perfusion.
Assuntos
Circulação Coronária/efeitos dos fármacos , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Óxido Nítrico/biossíntese , Relaxina/farmacologia , Acetilcolina/farmacologia , Animais , Endotélio Vascular/fisiologia , Cobaias , Técnicas In Vitro , L-Lactato Desidrogenase/metabolismo , Masculino , Contração Miocárdica/efeitos dos fármacos , Nitroprussiato/farmacologia , Ratos , Ratos Wistar , Estimulação Química , Vasodilatadores/farmacologiaRESUMO
This study shows that specialized contractile endothelial cells exist in rat liver sinusoids which may be involved in the local control of hemodynamics and which are sensitive to vasoactive agents, including the vasorelaxant hormone relaxin. Male rats were treated with 10 microg relaxin for 4 days; phosphate-buffered saline (PBS)-treated rats were the controls. For comparison, rats treated with relaxin together with the NO-synthase inhibitor N(omega)-nitro-l -arginine methyl ester (L-NAME), and rats treated with the vasodilator taurodeoxycholic acid or the vasoconstrictor ethanol were investigated. Liver fragments were studied morphologically and morphometrically. In the control rats, peculiar contractile cells were present in the endothelial lining. These cells had abundant myofilaments and formed cytoplasmic blebs projecting into and often occluding the lumen. In the ethanol-treated rats, sinusoids were constricted and filled with cytoplasmic blebs. In the relaxin-treated rats, sinusoids were markedly dilated and the cytoplasmic blebs nearly disappeared. Similar findings were observed in the taurodeoxycholic acid-treated rats. The effects of relaxin were blunted by L-NAME, suggesting that the relaxin action involves an NO-mediated mechanism.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/ultraestrutura , Circulação Hepática/efeitos dos fármacos , Relaxina/farmacologia , Vasodilatadores/farmacologia , Animais , Fígado/ultraestrutura , Masculino , Microcirculação/ultraestrutura , Microscopia Eletrônica , Ratos , Ratos Sprague-DawleyRESUMO
The effects of RLX on the microvasculature of the mouse mammary gland are reported. RLX (pure porcine standard NIH-RXN-P1) at a dose of 3 GPU was administered subcutaneously to virgin adult mice ovariectomized 12 days before. The mammary glands were removed 18-20 h after RLX injection and their examination by light microscopy did not reveal any substantial growth-response to the hormone. Histology and morphometry indicated striking dilation of microvessels, especially capillaries, and electron microscopy revealed an increase in the micropinocytotic vesicles, thus suggesting enhanced transendothelial transport of substances. Such phenomena, which were independent of a release of granules by mast cells, may represent an important component of the mammotrophic action of RLX.
Assuntos
Glândulas Mamárias Animais/efeitos dos fármacos , Relaxina/farmacologia , Animais , Feminino , Glândulas Mamárias Animais/irrigação sanguínea , Camundongos , Microcirculação/efeitos dos fármacos , Microcirculação/ultraestrutura , Microscopia EletrônicaRESUMO
Previous studies showed that the hormone relaxin acts on human breast cancer MCF-7 cells in vitro by modulating cell proliferation and promoting cell differentiation toward a duct epithelial phenotype. The present study was designed to investigate whether relaxin retains these properties when acting in vivo on MCF-7 cell tumors developed in athymic nude mice. Mice bearing MCF-7 cell tumors transplanted under the mammary fat pad and estrogenized to sustain tumor growth were treated systemically with relaxin (10 microg/day) for 19 days. Vehicle-treated mice were used as controls. Thirty days later, the mice were sacrificed and tumor fragments were analyzed by light and electron microscopy and immunocytochemistry. Measurements of tumor volume were recorded weekly for the overall experimental period. The results obtained indicate that relaxin treatment promotes differentiation of tumor cells towards both myoepithelial-like and epithelial-like cells, as judged by the ultrastructural features of the cells and by the increased expression of smooth muscle actin and cadherins. Measurements of tumor size and of the number of cycling cells show that relaxin, at the doses and times of exposure used in this study, does not significantly influence tumor growth and cell proliferation.