Trabajo presentado al 8th Forum of Neuroscience (FENS) celebrado en Barcelona del 14 al 18 de jul... more Trabajo presentado al 8th Forum of Neuroscience (FENS) celebrado en Barcelona del 14 al 18 de julio de 2012.
Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative d... more Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular–brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain–cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animal...
Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26–28 cont... more Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26–28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3–4 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric oxide synthase (NOS) isoforms and oxidative stress levels were assessed. Ascending aortas from young adult CD mice showed moderate (50%) luminal stenosis, whereas endothelial function and oxidative stress were comparable to wild-type. CD mice showed greater contractions to KCl. However, α1-adrenergic contractions to phenylephrine, but not with a thromboxane analogue, were compromised. Decreased phenylephrine responses were not affected by selective inducible NOS blockade with 1400 W, but were p...
AimIncreased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/... more AimIncreased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium‐derived hyperpolarization (EDH). We investigated whether EDH‐type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influence of peroxynitrite.MethodsVascular function was determined by wire myography after TP stimulation with the thromboxane A2 mimetic 9,11‐dideoxy‐9α, 11α ‐methano‐epoxy prostaglandin F2α (U46619) in MCA of Sprague Dawley rats subjected to MCA occlusion (90 min)/reperfusion (24 h) or sham operation, and in non‐operated (control) rats. Some rats were treated with saline or the peroxynitrite decomposition catalyst 5,10,15,20‐tetrakis(4‐sulfonatophenyl)porphyrinato iron (III) (20 mg kg−1). Protein expression was evaluated in MCA and in human microvascular endothelial cells submitted to hypoxia (overnight)/reoxygenation (24 h) (H/R) using immunofl...
Greater understanding of the cellular arrangement in the vascular wall and receptor mediated cell... more Greater understanding of the cellular arrangement in the vascular wall and receptor mediated cell-cell communication is crucial to the design of new drugs for treating cardiovascular disease. VASCAN 2000 is an EC funded partnership comprising vascular biologists, imaging scientists and software companies. In order to develop methods of studying vascular structure and function simultaneously in live tissue we are considering; (i) segmentation methods and morphometric analysis; (ii) point spread function (psf) measurement and deconvolution; (iii) non-biased counting; (iv) fast Fourier transform (FFT) analysis of 2D and 3D data; and (v) visualisation. Here we outline some of our progress to date.
We have previously developed a method for estimating elastin content and organization in resistan... more We have previously developed a method for estimating elastin content and organization in resistance arteries, where it is a minor component. The aim of the present study was to validate the method against a quantitative assay and to determine the relative importance of elastin content and organization for intrinsic elasticity of small arteries. Mesenteric third order branches (from 10-day-old, 1- and 6-month-old rats) and middle cerebral arteries (from 6-month-old rats) were pressurized. beta-Values were calculated from stress-strain relationships and used as indicators of intrinsic stiffness. The same pressure-fixed arteries were used to estimate elastin content and organization in the internal elastic lamina with confocal microscopy. Collagen and elastin contents were determined by Picrosirius Red staining and radioimmunoassay for desmosine, respectively. Confocal and desmosine assays gave similar results: no difference in elastin content of mesenteric vessels from 1- and 6-month-old rats, and a significant reduction in cerebral compared to mesenteric arteries. For all parameters (elastin and collagen content, fenestrae area and internal elastic lamina thickness) the best correlation was found between beta-values and fenestrae size. These data suggest that in small arteries: (1) confocal microscopy can be used as a method for the simultaneous study of changes in elastin content and organization; and (2) elastin organization might be a key determinant of intrinsic elastic properties.
Background and PurposeTo analyse the relative contribution of β1‐, β2‐ and β3‐adrenoceptors (Adrb... more Background and PurposeTo analyse the relative contribution of β1‐, β2‐ and β3‐adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways.Experimental ApproachRat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real‐time‐PCR and immunohistochemistry, and for the pharmacological characterization of Adrb‐mediated activity by wire myography and tissue nucleotide accumulation.Key ResultsThe mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β1, β2), CGP20712A (β1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β2), SR59230A (β3), ODQ (soluble guanylyl cyclase inhibitor), L‐NAME or endothelium removal. In aorta, Adrb...
American Journal of Physiology-Heart and Circulatory Physiology, 2007
Transient focal cerebral ischemia in the rat alters vessel properties, and spontaneously hyperten... more Transient focal cerebral ischemia in the rat alters vessel properties, and spontaneously hypertensive rats (SHR) show a poorer outcome after ischemia. In the present study we examined the role of hypertension on vessel properties after ischemia-reperfusion. The right middle cerebral artery (MCA) was occluded (90 min) and reperfused (24 h) in SHR ( n = 12) and Wistar-Kyoto rats (WKY; n = 11). Sham-operated rats (SHR, n = 10; WKY, n = 10) were used as controls. The structural, mechanical, and myogenic properties of the MCA were assessed by pressure myography. Nuclei distribution and elastin content and organization were analyzed by confocal microscopy. Infarct volume was larger in SHR than in WKY rats. Ischemia-reperfusion induced adventitial hypertrophy associated with an increase in the total number of adventitial cells. In addition, fenestrae area and arterial distensibility increased and myogenic tone decreased in the MCA of WKY rats after ischemia-reperfusion. Hypertension per se...
American Journal of Physiology-Heart and Circulatory Physiology, 2006
Resistance artery narrowing and stiffening are key elements in the pathogenesis of essential hype... more Resistance artery narrowing and stiffening are key elements in the pathogenesis of essential hypertension, but their origin is not completely understood. In mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR), we have shown that inward remodeling is associated with abnormal elastic fiber organization, leading to smaller fenestrae in the internal elastic lamina. Our current aim is to determine whether this alteration is an early event that precedes vessel narrowing, or if elastic fiber reorganization in SHR arteries occurs because of the remodeling process itself. Using MRA from 10-day-old, 30-day-old, and 6-mo-old SHR and normotensive Wistar Kyoto rats, we investigated the time course of the development of structural and mechanical alterations (pressure myography), elastic fiber organization (confocal microscopy), and amount of elastin (radioimmunoassay for desmosine) and collagen (picrosirius red). SHR MRA had an impairment of fenestrae enlargement durin...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the ass... more Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-α, IL-1β, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and a...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
This study was performed to investigate the role of reactive oxygen species and inducible nitric ... more This study was performed to investigate the role of reactive oxygen species and inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) metabolites in the lipopolysaccharide effect on bradykinin-induced relaxation in middle cerebral arteries from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). LPS exposure (10 μg/ml for 1–5 h) reduced bradykinin relaxation; this effect appeared earlier and was greater in arteries from SHR than WKY rats. LPS also reduced the relaxation to the NO donor diethylamine (DEA)-NO; however, LPS modified neither the bradykinin relaxation after inhibiting NO synthesis with NG-monomethyl-l-arginine (0.1 mM) nor endothelial NOS expression. In arteries from WKY rats, the respective iNOS and COX-2 inhibitors aminoguanidine (0.1 mM) and NS-398 (10 μM) and the superoxide anion scavenger SOD (100 U/ml) reduced the LPS effect on bradykinin relaxation; however, the thromboxane A2(TxA2)PGH2receptor antagonist SQ-29548 (1...
Aerial parts (leaves, flowers, stem) of <i>Peperomia galioides</i> extract administer... more Aerial parts (leaves, flowers, stem) of <i>Peperomia galioides</i> extract administered to mice, was used to confirm its anti-inflammatory and sedative folk uses. The anti-inflammatory activity was assessed by croton oil-induced ear oedema and myeloperoxidase (acute inflammation); cotton pellet-induced granuloma (sub-acute inflammation) and <i>Escherichia coli</i> Lipopolysaccharide (LPS) induced inflammation (cellular mediators). The sedative activity was studied by the pentobarbital-induced sleeping time test. Single doses (300 and 600 mg/kg; i.p.) of the extract reduced croton oil-induced ear oedema and myeloperoxidase activity. Six days administration of the extract (300 mg/kg, i.p.) to mice implanted with cotton pellets diminished granuloma formation. LPS (20 mg/kg, i.p.) enhanced plasma nitrites and TNF-α levels that were inhibited by the extract. The duration but not the onset of sleeping time was enhanced by 300 and 600 mg/kg of the extract. Our resul...
SE HA ESTUDIADO EL MECANISMO DE ACCION DE 2 B-BLOQUEANTES UNO NO SELECTIVO (OXPRENOLOL) Y OTRO CA... more SE HA ESTUDIADO EL MECANISMO DE ACCION DE 2 B-BLOQUEANTES UNO NO SELECTIVO (OXPRENOLOL) Y OTRO CARDIOSELECTIVO (METOPROLOL) EN LA SINAPSIS ADRENERGICA PERIFERICA. EN EL TRATAMIENTO AGUDO EL OXPRENOLOL MOSTRO UNA CLARA AFINIDAD ANTAGONISTA POR LOS RECEPTORES . TANTO IN VIVO COMO IN VITRO. EL METOPROLOL CARECE DE CAPACIDAD ANTAGONISTA . POR OTRO LADO TRAS EL TRATAMIENTO PROLONGADO COM AMBOS EXISTE UNA DEPRESION DE LA RESPUESTA SIMPATICA PROBABLEMENTE POR UNA INHIBICION DE LOS RECEPTORES B-PRESINAPTICOS DADO QUE MIENTRAS LAS RESPUESTAS PRODUCIDAD POR ESTIMULACION NERVIOSA FUERON INHIBIDAS LAS PRODUCCIDAS POR NORADRENALINA NO FUERON MODIFICADAS. ADEMAS LA POBLACION PREDOMINANTE DE RECEPTORES B-PRESINAPTICOS VASCULARES PARECE PRETENDER AL SUBTIPO B2 MIENTRAS QUE LOS CARDIACOS PERTENECERIAN A LA SUBCLASE B1. FINALMENTE SE PONE DE MANIFIESTO UNA VEZ MAS LA IMPORTANCIA DE LA ADRENALINA LIBERADA POR LAS ADRENALES EN EL EFECTO INHIBIDOR DE ESTOS ANTAGONISTAS SOBRE LOS RECEPTORES BB-PRESINAPTI...
Trabajo presentado al 8th Forum of Neuroscience (FENS) celebrado en Barcelona del 14 al 18 de jul... more Trabajo presentado al 8th Forum of Neuroscience (FENS) celebrado en Barcelona del 14 al 18 de julio de 2012.
Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative d... more Life expectancy decreases with aging, with cardiovascular, mental health, and neurodegenerative disorders strongly contributing to the total disability-adjusted life years. Interestingly, the morbidity/mortality paradox points to females having a worse healthy life expectancy. Since bidirectional interactions between cardiovascular and Alzheimer’s diseases (AD) have been reported, the study of this emerging field is promising. In the present work, we further explored the cardiovascular–brain interactions in mice survivors of two cohorts of non-transgenic and 3xTg-AD mice, including both sexes, to investigate the frailty/survival through their life span. Survival, monitored from birth, showed exceptionally worse mortality rates in females than males, independently of the genotype. This mortality selection provided a “survivors” cohort that could unveil brain–cardiovascular interaction mechanisms relevant for normal and neurodegenerative aging processes restricted to long-lived animal...
Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26–28 cont... more Williams-Beuren syndrome (WBS) is a rare disorder caused by a heterozygous deletion of 26–28 contiguous genes that affects the brain and cardiovascular system. Here, we investigated whether WBS affects aortic structure and function in the complete deletion (CD) mouse model harbouring the most common deletion found in WBS patients. Thoracic aortas from 3–4 months-old male CD mice and wild-type littermates were mounted in wire myographs or were processed for histomorphometrical analysis. Nitric oxide synthase (NOS) isoforms and oxidative stress levels were assessed. Ascending aortas from young adult CD mice showed moderate (50%) luminal stenosis, whereas endothelial function and oxidative stress were comparable to wild-type. CD mice showed greater contractions to KCl. However, α1-adrenergic contractions to phenylephrine, but not with a thromboxane analogue, were compromised. Decreased phenylephrine responses were not affected by selective inducible NOS blockade with 1400 W, but were p...
AimIncreased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/... more AimIncreased thromboxane A2 and peroxynitrite are hallmarks of cerebral ischaemia/reperfusion (I/R). Stimulation of thromboxane/prostaglandin receptors (TP) attenuates endothelium‐derived hyperpolarization (EDH). We investigated whether EDH‐type middle cerebral artery (MCA) relaxations following TP stimulation are altered after I/R and the influence of peroxynitrite.MethodsVascular function was determined by wire myography after TP stimulation with the thromboxane A2 mimetic 9,11‐dideoxy‐9α, 11α ‐methano‐epoxy prostaglandin F2α (U46619) in MCA of Sprague Dawley rats subjected to MCA occlusion (90 min)/reperfusion (24 h) or sham operation, and in non‐operated (control) rats. Some rats were treated with saline or the peroxynitrite decomposition catalyst 5,10,15,20‐tetrakis(4‐sulfonatophenyl)porphyrinato iron (III) (20 mg kg−1). Protein expression was evaluated in MCA and in human microvascular endothelial cells submitted to hypoxia (overnight)/reoxygenation (24 h) (H/R) using immunofl...
Greater understanding of the cellular arrangement in the vascular wall and receptor mediated cell... more Greater understanding of the cellular arrangement in the vascular wall and receptor mediated cell-cell communication is crucial to the design of new drugs for treating cardiovascular disease. VASCAN 2000 is an EC funded partnership comprising vascular biologists, imaging scientists and software companies. In order to develop methods of studying vascular structure and function simultaneously in live tissue we are considering; (i) segmentation methods and morphometric analysis; (ii) point spread function (psf) measurement and deconvolution; (iii) non-biased counting; (iv) fast Fourier transform (FFT) analysis of 2D and 3D data; and (v) visualisation. Here we outline some of our progress to date.
We have previously developed a method for estimating elastin content and organization in resistan... more We have previously developed a method for estimating elastin content and organization in resistance arteries, where it is a minor component. The aim of the present study was to validate the method against a quantitative assay and to determine the relative importance of elastin content and organization for intrinsic elasticity of small arteries. Mesenteric third order branches (from 10-day-old, 1- and 6-month-old rats) and middle cerebral arteries (from 6-month-old rats) were pressurized. beta-Values were calculated from stress-strain relationships and used as indicators of intrinsic stiffness. The same pressure-fixed arteries were used to estimate elastin content and organization in the internal elastic lamina with confocal microscopy. Collagen and elastin contents were determined by Picrosirius Red staining and radioimmunoassay for desmosine, respectively. Confocal and desmosine assays gave similar results: no difference in elastin content of mesenteric vessels from 1- and 6-month-old rats, and a significant reduction in cerebral compared to mesenteric arteries. For all parameters (elastin and collagen content, fenestrae area and internal elastic lamina thickness) the best correlation was found between beta-values and fenestrae size. These data suggest that in small arteries: (1) confocal microscopy can be used as a method for the simultaneous study of changes in elastin content and organization; and (2) elastin organization might be a key determinant of intrinsic elastic properties.
Background and PurposeTo analyse the relative contribution of β1‐, β2‐ and β3‐adrenoceptors (Adrb... more Background and PurposeTo analyse the relative contribution of β1‐, β2‐ and β3‐adrenoceptors (Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/cGMP signalling pathways.Experimental ApproachRat mesenteric resistance artery (MRA) and aorta were used to analyse the Adrb expression by real‐time‐PCR and immunohistochemistry, and for the pharmacological characterization of Adrb‐mediated activity by wire myography and tissue nucleotide accumulation.Key ResultsThe mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells (SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β1, β2), CGP20712A (β1), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β2), SR59230A (β3), ODQ (soluble guanylyl cyclase inhibitor), L‐NAME or endothelium removal. In aorta, Adrb...
American Journal of Physiology-Heart and Circulatory Physiology, 2007
Transient focal cerebral ischemia in the rat alters vessel properties, and spontaneously hyperten... more Transient focal cerebral ischemia in the rat alters vessel properties, and spontaneously hypertensive rats (SHR) show a poorer outcome after ischemia. In the present study we examined the role of hypertension on vessel properties after ischemia-reperfusion. The right middle cerebral artery (MCA) was occluded (90 min) and reperfused (24 h) in SHR ( n = 12) and Wistar-Kyoto rats (WKY; n = 11). Sham-operated rats (SHR, n = 10; WKY, n = 10) were used as controls. The structural, mechanical, and myogenic properties of the MCA were assessed by pressure myography. Nuclei distribution and elastin content and organization were analyzed by confocal microscopy. Infarct volume was larger in SHR than in WKY rats. Ischemia-reperfusion induced adventitial hypertrophy associated with an increase in the total number of adventitial cells. In addition, fenestrae area and arterial distensibility increased and myogenic tone decreased in the MCA of WKY rats after ischemia-reperfusion. Hypertension per se...
American Journal of Physiology-Heart and Circulatory Physiology, 2006
Resistance artery narrowing and stiffening are key elements in the pathogenesis of essential hype... more Resistance artery narrowing and stiffening are key elements in the pathogenesis of essential hypertension, but their origin is not completely understood. In mesenteric resistance arteries (MRA) from spontaneously hypertensive rats (SHR), we have shown that inward remodeling is associated with abnormal elastic fiber organization, leading to smaller fenestrae in the internal elastic lamina. Our current aim is to determine whether this alteration is an early event that precedes vessel narrowing, or if elastic fiber reorganization in SHR arteries occurs because of the remodeling process itself. Using MRA from 10-day-old, 30-day-old, and 6-mo-old SHR and normotensive Wistar Kyoto rats, we investigated the time course of the development of structural and mechanical alterations (pressure myography), elastic fiber organization (confocal microscopy), and amount of elastin (radioimmunoassay for desmosine) and collagen (picrosirius red). SHR MRA had an impairment of fenestrae enlargement durin...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the ass... more Cytokine levels are elevated in many cardiovascular diseases and seem to be implicated in the associated disturbances in vascular reactivity reported in these diseases. Arterial blood pressure is maintained within a normal range by changes in peripheral resistance and cardiac output. Peripheral resistance is mainly determined by small resistance arteries and arterioles. This review focuses on the effects of cytokines, mainly TNF-α, IL-1β, and IL-6, on the reactivity of resistance arteries. The vascular effects of cytokines depend on the balance between the vasoactive mediators released under their influence in the different vascular beds. Cytokines may induce a vasodilatation and hyporesponsiveness to vasoconstrictors that may be relevant to the pathogenesis of septic shock. Cytokines may also induce vasoconstriction or increase the response to vasoconstrictor agents and impair endothelium-dependent vasodilatation. These effects may help predispose to vessel spasm, thrombosis, and a...
American Journal of Physiology-Heart and Circulatory Physiology, 2004
This study was performed to investigate the role of reactive oxygen species and inducible nitric ... more This study was performed to investigate the role of reactive oxygen species and inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) metabolites in the lipopolysaccharide effect on bradykinin-induced relaxation in middle cerebral arteries from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). LPS exposure (10 μg/ml for 1–5 h) reduced bradykinin relaxation; this effect appeared earlier and was greater in arteries from SHR than WKY rats. LPS also reduced the relaxation to the NO donor diethylamine (DEA)-NO; however, LPS modified neither the bradykinin relaxation after inhibiting NO synthesis with NG-monomethyl-l-arginine (0.1 mM) nor endothelial NOS expression. In arteries from WKY rats, the respective iNOS and COX-2 inhibitors aminoguanidine (0.1 mM) and NS-398 (10 μM) and the superoxide anion scavenger SOD (100 U/ml) reduced the LPS effect on bradykinin relaxation; however, the thromboxane A2(TxA2)PGH2receptor antagonist SQ-29548 (1...
Aerial parts (leaves, flowers, stem) of <i>Peperomia galioides</i> extract administer... more Aerial parts (leaves, flowers, stem) of <i>Peperomia galioides</i> extract administered to mice, was used to confirm its anti-inflammatory and sedative folk uses. The anti-inflammatory activity was assessed by croton oil-induced ear oedema and myeloperoxidase (acute inflammation); cotton pellet-induced granuloma (sub-acute inflammation) and <i>Escherichia coli</i> Lipopolysaccharide (LPS) induced inflammation (cellular mediators). The sedative activity was studied by the pentobarbital-induced sleeping time test. Single doses (300 and 600 mg/kg; i.p.) of the extract reduced croton oil-induced ear oedema and myeloperoxidase activity. Six days administration of the extract (300 mg/kg, i.p.) to mice implanted with cotton pellets diminished granuloma formation. LPS (20 mg/kg, i.p.) enhanced plasma nitrites and TNF-α levels that were inhibited by the extract. The duration but not the onset of sleeping time was enhanced by 300 and 600 mg/kg of the extract. Our resul...
SE HA ESTUDIADO EL MECANISMO DE ACCION DE 2 B-BLOQUEANTES UNO NO SELECTIVO (OXPRENOLOL) Y OTRO CA... more SE HA ESTUDIADO EL MECANISMO DE ACCION DE 2 B-BLOQUEANTES UNO NO SELECTIVO (OXPRENOLOL) Y OTRO CARDIOSELECTIVO (METOPROLOL) EN LA SINAPSIS ADRENERGICA PERIFERICA. EN EL TRATAMIENTO AGUDO EL OXPRENOLOL MOSTRO UNA CLARA AFINIDAD ANTAGONISTA POR LOS RECEPTORES . TANTO IN VIVO COMO IN VITRO. EL METOPROLOL CARECE DE CAPACIDAD ANTAGONISTA . POR OTRO LADO TRAS EL TRATAMIENTO PROLONGADO COM AMBOS EXISTE UNA DEPRESION DE LA RESPUESTA SIMPATICA PROBABLEMENTE POR UNA INHIBICION DE LOS RECEPTORES B-PRESINAPTICOS DADO QUE MIENTRAS LAS RESPUESTAS PRODUCIDAD POR ESTIMULACION NERVIOSA FUERON INHIBIDAS LAS PRODUCCIDAS POR NORADRENALINA NO FUERON MODIFICADAS. ADEMAS LA POBLACION PREDOMINANTE DE RECEPTORES B-PRESINAPTICOS VASCULARES PARECE PRETENDER AL SUBTIPO B2 MIENTRAS QUE LOS CARDIACOS PERTENECERIAN A LA SUBCLASE B1. FINALMENTE SE PONE DE MANIFIESTO UNA VEZ MAS LA IMPORTANCIA DE LA ADRENALINA LIBERADA POR LAS ADRENALES EN EL EFECTO INHIBIDOR DE ESTOS ANTAGONISTAS SOBRE LOS RECEPTORES BB-PRESINAPTI...
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