RESUMEN
1. The mechanisms of the sustained vasodilator actions of corticotrophin-releasing factor (CRF) and sauvagine (SVG) were studied using rings of endothelium de-nuded rat thoracic aorta (RTA) and the isolated perfused rat superior mesenteric arterial vasculature (SMA). 2. SVG was approximately 50 fold more potent than CRF on RTA (EC40: 0.9 +/- 0.2 and 44 +/- 9 nM respectively, P < 0.05), and approximately 10 fold more active in the perfused SMA (ED40: 0.05 +/- 0.02 and 0.6 +/- 0.1 nmol respectively, P < 0.05). Single bolus injections of CRF (100 pmol) or SVG (15 pmol) in the perfused SMA caused reductions in perfusion pressure of 23 +/- 1 and 24 +/- 2% that lasted more than 20 min. 3. Removal of the endothelium in the perfused SMA with deoxycholic acid attenuated the vasodilatation and revealed two phases to the response; a short lasting direct action, and a sustained phase which was fully inhibited. 4. Inhibition of nitric oxide synthase with L-NAME (100 microM) L-NMMA (100 microM) or 2-ethyl-2-thiopseudourea (ETPU, 100 microM) had similar effects on the vasodilator responses to CRF as removal of the endothelium, suggesting a pivotal role for nitric oxide. However the selective guanylate cyclase inhibitor 1H-[l,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one (ODQ, 10 microM) did not affect the response to CRF. 5. High potassium (60 mM) completely inhibited the vasodilator response to CRF in the perfused SMA, indicating a role for K channels in this response. 6. Compared to other vasodilator agents acting via the release of NO, the actions of CRF and SVG are strikingly long-lasting, suggesting a novel mechanism of prolonged activation of nitric oxide synthase.
Asunto(s)
Hormona Liberadora de Corticotropina/farmacología , Endotelio/fisiología , Óxido Nítrico/metabolismo , Péptidos/farmacología , Vasodilatadores/farmacología , Acetilcolina/farmacología , Proteínas Anfibias , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/fisiología , Ácido Desoxicólico/farmacología , Detergentes/farmacología , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Gliburida/farmacología , Hipoglucemiantes/farmacología , Técnicas In Vitro , Masculino , Arterias Mesentéricas/efectos de los fármacos , Arterias Mesentéricas/fisiología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo III , Nitroprusiato/farmacología , Hormonas Peptídicas , Bloqueadores de los Canales de Potasio , Cloruro de Potasio/farmacología , Ratas , Ratas Wistar , Tetraetilamonio/farmacología , Tiourea/análogos & derivados , Tiourea/farmacología , Vasodilatación/efectos de los fármacos , omega-N-Metilarginina/farmacologíaRESUMEN
In vitro corticotrophin releasing factor (CRF) causes a prolonged endothelium-dependent vasodilatation which is blocked by inhibitors of nitric oxide (NO) synthase (NOS). Here the role of NO in CRF-induced reductions in blood pressure (BP) has been investigated using anaesthetised rats. Infusion of NG-Nitro-L-arginine Methyl Ester (L-NAME) increased mean arterial pressure (MAP) but did not reduce the fall in BP caused by CRF injection. Bolus injection of L-NAME produced a marked vasopressor effect when given alone. However, when administered 20 min after CRF, L-NAME restored MAP to basal levels, but the marked vasopressor response observed in control animals was completely blocked. This indicates that the increase in BP occurring on bolus injection of L-NAME is not simply due to an inhibition of NO-dependent vasodilatation.
Asunto(s)
Hormona Liberadora de Corticotropina/farmacología , Inhibidores Enzimáticos/farmacología , Hipertensión/prevención & control , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/metabolismo , Anestesia , Animales , Modelos Animales de Enfermedad , Interacciones Farmacológicas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Hipertensión/fisiopatología , Masculino , NG-Nitroarginina Metil Éster/metabolismo , Ratas , Ratas Wistar , Valores de Referencia , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiologíaRESUMEN
This paper describes and compares two methods used to assign exposure categories to 10,766 petroleum refinery employees included in an epidemiological study. The first scheme grouped individuals into six organization (OR) job groups: Administrative, Maintenance, Operations, Laboratory, General and Other. This scheme used "most common administrative department," as determined by computerized job histories. For the second classification scheme, "most common job title" and "most common plant location" were used to group individuals in four ways (IH codes): 1)job type (administrative, maintenance, operations and unknown); 2) contact with refinery processes; 3) exposure to light aromatics; and 4) exposure to heavy oils. Exposure categories for the latter three were none, occasional, routine and unknown. Comparison of the two schemes showed that OR job groups developed from administrative job histories were sometimes useful in classifying employees according to refinery exposures. While OR job groups were acceptable for employees clearly in managerial, maintenance or operations positions, IH codes provided more precise exposure profiles for these three relatively homogeneous groups. For individuals in laboratory positions and those with vague or unspecified department codes (23% of this cohort), the IH classification codes were necessary to group employees by job and exposure.
Asunto(s)
Industrias , Mortalidad , Petróleo , Humanos , Estudios RetrospectivosRESUMEN
Localization of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in alveoli of salivary glands of female Amblyomma americanum (L.) was accomplished with an indirect immunofluorescent technique. Little cyclic AMP fluorescence was seen in Type I alveoli in glands of unfed females but considerable fluorescence was seen in Type I alveoli of glands obtained from females that had fed. The most intense cyclic AMP fluorescence was observed in complex granular cells of Type II and III alveoli in glands of unfed females and glands from females in early stages of tick feeding. In the latter stages of tick feeding an increase in fluorescence in Type III alveoli was observed in cells near the lumen, possibly adluminal interstitial or transformed granular cells.
Asunto(s)
AMP Cíclico/análisis , Garrapatas/análisis , Animales , Dopamina/farmacología , Ingestión de Alimentos , Femenino , Técnica del Anticuerpo Fluorescente , Glándulas Salivales/análisis , Glándulas Salivales/fisiología , Garrapatas/fisiologíaRESUMEN
We have investigated the membranes of erythrocytes from a family in which there is a genetic defect [previously described as the En[a-] condition[ resulting in the loss of the major erythrocyte sialoglycoprotein [PAS-i]. The results show that two different types of sialoglycoprotein deficiency can be distinguished within this family. We suggest that the En[a-] group of variants is more appropriately described as a class of sialoglycoprotein deficient erythrocytes. Using a new technique it is shown that the blood group M antigen of normal erythrocytes is found only on the erythrocyte sialoglycoprotein while in this family the M antigen is found on membrane components other than the sialoglycoprotein. Our results suggest that the amino acid sequence of the sialoglycoprotein is important in defining the difference between the blood group M and N antigens in normal erythrocytes.
Asunto(s)
Membrana Eritrocítica/análisis , Eritrocitos/análisis , Enfermedades Genéticas Congénitas , Glicoforinas/deficiencia , Sistema del Grupo Sanguíneo MNSs , Sialoglicoproteínas/deficiencia , Ácido Aminosalicílico/metabolismo , Antígenos de Grupos Sanguíneos , Electroforesis en Gel de Poliacrilamida , Membrana Eritrocítica/metabolismo , Femenino , Humanos , Lectinas/farmacología , Masculino , Proteínas de la Membrana/análisis , LinajeRESUMEN
The dependence of the (Na-++K-+)-dependent ATPase (adenosine triphosphatase) (EC 3.6.1.3) on lipid has been examined in a number of different ways, with the use of various preparations from kidney tissue. The main findings were as follows. (1) The ATPase activities of the preparations examined were closely correlated with their total phospholipid content. (2) Extraction of the ATPase with deoxycholate or Lubrol W, combined with suitable salt-fractionation and washing procedures, removed phospholipid, cholesterol and enzymic activity in parallel; but activity was completely lost before all lipid had been removed. (3) The loss of activity could not be attributed to inhibition by residual detergent. (4) No selective removal of any particular phospholipid class by detergent could be detected. (5) Consistent reactivation of the Lubrol-extracted enzymes was obtained by adding dispersions of exogenous phospholipid, but only some, bearing a net negative charge, such as phosphatidylserine and phosphatidylglycerol, were effective. (6) The degree of reactivation was correlated with the amount of residual activity remaining after lipid depletion. (7) Partial purification of the ATPase, giving a 50-fold increase in specific activity, was not accompanied by selective enhancement of any particular class of phospholipid. We conclude that although the ATPase is dependent on phospholipid, only the reactivation results provide evidence for specificity.