Gustavo Guevara‐Balcázar

Instituto Politécnico Nacional

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María del Carmen Castillo‐Hernández

Instituto Politécnico Nacional

Eleazar Lara‐Padilla

Instituto Politécnico Nacional

Alexander Kormanovski

Instituto Politécnico Nacional

Maria Carmen Castillo‐Hernandez

Instituto Politécnico Nacional

M.C. Castillo-Hernandez

Instituto Politécnico Nacional

Ivan Rubio‐Gayosso

Instituto Politécnico Nacional

Antonio Franco‐Vadillo

Instituto Politécnico Nacional

Cleva Villanueva

Instituto Politécnico Nacional

Carlos Castillo‐Henkel

Instituto Politécnico Nacional

Mireille Toledo-Blas

Instituto Politécnico Nacional

Cooperative Institutions

Instituto Politécnico Nacional

111

Tecnológico Nacional de México

Mexican Social Security Institute

Center for Research and Advanced Studies of the National Polytechnic Institute

Centro Medico Nacional Siglo XXI

Instituto Nacional de Cardiología

Universidad Nacional Autónoma de México

Hospital de Especialidades

Instituto Nacional de Perinatología

Medicina

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Cannabidiol‐mediated RISK PI3K/AKT and MAPK/ERK pathways decreasing reperfusion myocardial damage

Pharmacology Research & Perspectives (2021)

Antonio Franco‐Vadillo Mireille Toledo‐Blass Zeltzin Rivera‐Herrera Gustavo Guevara‐Balcázar Oscar Orihuela

Abstract Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional damage to ischemic myocardial tissue; this forces to seek therapies of cardioprotection to reduce this additional damage. There are many cardioprotective agents; within these, cannabinoids have shown to have beneficial effects, mainly cannabidiol (CBD). CBD is a non psychoactive cannabinoid. To evaluate the effect in experimental models of CBD in myocardial ischemia reperfusion in rats, twelve‐week‐old male rats have been used. The animals were divides in 3 groups: control(C), ischemia reperfusion (IR) and CBD pretreatment (1/day/5mg/kg /10days). Langendorff organ isolate studies were performed, and the area of infarction was assessed with triphenyl tetrazolium, in addition to molecular analysis of AT1 and AT2 receptors and Akt and Erk proteins and their phosphorylated forms related to RISK pathways. It was observed that there is an improvement with the use of CBD increasing inotropism and cardiac lusitropism, improving considerably the cardiovascular functionality. These could be related to the reduction of the area of infarction and activation of the AT2 receptor and the RISK pathway with absence of activation of the AT2 receptor (these could relate the reduction of the infarct area and the restoration of cardiovascular function with the activation of the AT2 receptor and the RISK pathway with the absence of activation of the AT2 receptor). The use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.

Cardioprotection

10.1002/prp2.784

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Mannose polymer induces vasodilation through a luminal mannose receptor in rat mesenteric arteries

Frontiers in bioscience (2008)

Gustavo Guevara‐Balcázar Iván Rubio-Gayosso Ángel Miliar-García Carmen Castillo Israel Ramírez‐Sánchez

Several of the luminal endothelial glycocalyx functions are exerted via interactions with glycosidic components and sugar binding proteins with lectinic activity. One important example is the mannose receptor (MR). The MR has been detected in cell types that mediate the phagocytosis and pinocytosis of particles and solutes containing mannose. Using isolated constant pressurized rat mesenteric arteries (RMA), we evaluated the effects of a mannose polymer in the vascular tone. RMA were pre-contracted with 10µmol/L phenylephrine and carbohydrates were perfused at 20µl/min. Perfusion of free D-mannose [1nmol/L to100µmol/L] induced a concentration-dependent vasodilation of pre-contracted RMA. Perfusion of mannose polymer [1nmol/L to 100µmol/L] induced a larger effect in a concentration-dependent vasodilation. Mannose polymer's maximum effect reached a 96% of basal diameter; this significant vasodilation was not nitric oxide (NO) or cyclooxygenase (COX) dependent effect. We corroborated the binding of the mannose polymer to the endothelial lumen, by perfusion of a fluorescently labeled mannose polymer; and also, we detected a significant level of MR mRNA in whole mesenteric arteries. With all these, we proposed a novel effect of a MR in the regulation of vascular tone.

Mannose receptor

Mesenteric arteries

10.2741/3081

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Reactivity changes in coronary artery and thoracic aorta in the gene mutant mice sgcd (B6.129 Sgcdtm1Mcn)

The FASEB Journal (2012)

Maria Carmen Marin-Romero Gustavo Guevara‐Balcázar Haydeé Rosas Ramón Mauricio Coral‐Vázquez Rosa A. Bobadilla-Lugo

Objective Study of cardiovascular reactivity changes in the gene mutant mice sgcd. Introduction Deletion of d‐sarcoglicano gene (delta‐SG) is related with structural and functional changes of squeletical, smooth and cardiac muscle which are related with limb‐girdle muscular dystrophy and cardiomiopathy. In this work we study the effect of some contractile and vasodilator agonist like angiotensin II and acethylcholine in this experimental model of dystrophy. Methods We used wild‐type and Knock‐out 5 months old female mice. We obtain thoracic aorta and the heart and both were immediately excised and placed in cold buffer, cleaned and freed from surrounding connective tissue. Isolated aortic rings and Langendorff system were maintained at 37° C, pH 7.4, were and bubbled with a mixture of 95% O 2 and 5% CO 2 . After that we probe angiotnesin II (10 −9 a 10 −6 M) with and without L‐NAME( sNOS antagonist) and indomethacin (COX‐1 and COX‐2 antagonist ). Results and conclusions We obtein significant differences between wild type and knock‐out mice, in the knock‐out mice we found an increase in the response of angiotensin II for that reason we suggest the participation of one contractile prostanoid in this effect. For that reason we decide to inhibit the contractile effect of angiotensin II with indometacin and the result was the inhibition of the contractile response. In other hand we analyse the vasodilator effect of acethylcholine at different concentrations and the result was less vasodilator effect in knock‐out mice, however we did not have differences in the vasodilator effect of nitroprusiate between wild type and knock‐out.

Wild type

Thoracic aorta

Knockout mouse

10.1096/fasebj.26.1_supplement.1115.7

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Spermine-induced negative inotropic effect in isolated rat heart, is mediated through the release of ATP

Biochemical Pharmacology (2003)

Gustavo Guevara‐Balcázar Enrique Querejeta Oskar Nuevo-Adalla Alejandra Orozco-Guillén Iván Rubio-Gayosso

Polyamine

10.1016/s0006-2952(03)00238-7

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Oxidative stress and vascular reactivity changes in thoracic and abdominal aorta expose at the hyperbaric oxygenation (693.1)

The FASEB Journal (2014)

Nallely Acevedo‐Villavicencio Alexander Kormanovsky Cleva Villanueva Israel Ramírez‐Sánchez Eleazar Lara‐Padilla

During the hyperbaric oxygenation therapy (HBO) has been described some changes like hypoglycemia, low blood pressure, etc. The mean idea of this work is to analyze if the HBO induce some changes in the vascular reactivity and oxidative stress in healthy rats. Methods: Male rats were used (3 months old) and divided in 2 groups: with and without HBO.Rats were exposed to pure oxygen at 2 absolute atmospheres during 60 min for 3, 5, 10 and 20 sessions, after that, we obtain thoracic and abdominal aorta and were used some of the aortic rings for the isolated organ system where we made concentration response curves; and other aortic rings were used to analyze the oxidative stress. Results: changes were observed in the contractile effect to phenyleprine in both segments after HBO, without any changes in the relaxant response. On the other hand thoracic oxidative response were higher after 3 sessions of HBO, but in an interesting way we can observe that antioxidant enzyme decreased after this time; those results suggest that the antioxidant system increase the response trying to metabolize O2. Grant Funding Source : COFAA / IPN

Abdominal aorta

Thoracic aorta

Hyperbaric oxygenation

Reactivity

10.1096/fasebj.28.1_supplement.693.1

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Comparative treatment with hyperbaric oxygen therapy in a model of systemic loxoscelism in rats.

DOAJ (DOAJ: Directory of Open Access Journals) (2022)

Mireille Toledo-Blas Antonio Franco‐Vadillo Selma Alin Somilleda-Ventura Brenda Dominguez-Ruiz Gustavo Guevara‐Balcázar

Spiders of the Loxosceles genus, known as violin spiders, produce venom with dermonecrotic and systemic effects, as it is a species widely distributed in the world, its study represents a high medical relevance. Systemic loxoscelism, which occurs in 1 in 5 cases and is the most frequent in children, can be fatal, so the study of effective therapy is of great relevance. In the present study, we compared different therapeutic options to mitigate the systemic effects of Loxosceles boneti venom in a model in which prepubertal rats were used.A model of systemic intoxication by L. boneti venom was provoked in male Wistar rats. Study groups were formed: healthy control, with venom and untreated control, treatment with N-acetylcysteine, and/or hyperbaric oxygenation therapy. Subsequently, pathological analysis of the kidney and lung was performed. The oxidant-antioxidant response was evaluated, and molecular analysis of the COX-1 and COX-2 enzymes was performed.Regenerative changes were observed at the cellular level in both treatments, being more noticeable in the hyperbaric oxygen therapy (HBO) group. The anti-oxidant response was outstanding in the same group.Both treatments offer considerable benefits, however; further studies are needed to provide adequate therapeutics.

Hyperbaric oxygenation

Therapeutic effect

Antidote

10.22038/ijbms.2022.65357.14385

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Changes during development of COX 1 and 2 in heart, abdominal and thoracic aorta (837.11)

The FASEB Journal (2014)

Nallely Acevedo‐Villavicencio Mónica Arellano Israel Ramírez‐Sánchez Elvia Mera‐Jimenez Emilio Lopez‐Calderon

Cyclooxigenase 1 and 2 have been related in the release of prostanoids that regulate the effect of various agonists as in the case of phenylephrine, but its unknown that how this enzyme is involved in the contractile response to phenylephrine age‐dependent. The aim of this paper is to analyze changes of COX 1 and 2 involvements in the contractile response to phenylephrine in the thoracic and abdominal aorta and coronary artery of pubescent, young and old rats. It has been describe that during development there are changes in the activity of some enzymatic pathways, in this work we analyze the change in the involvement of cyclooxygenase and PGs in the contractile effect of phenylephrine with age. Methods: we used male rats of 6, 16 weeks and 1 year of age. Rats were anesthetized with pentobarbital (50 mg / kg), after that we proceeded to obtain the thoracic aorta and abdominal aorta and the heart and they were placed in an isolated organ system where we proceeded to make concentration response curves to phenylephrine. On the other hand we obtain heart and aorta for the western blot analysis and the immunohistochemistry assay of COX 1 and COX 2. Conclusions: COX1 increase during development. On the other hand COX2 decrease in the elderly stage only in thoracic aorta. Grant Funding Source : COFAA / IPN

Phenylephrine

Abdominal aorta

Thoracic aorta

10.1096/fasebj.28.1_supplement.837.11

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Changes in the expression and function of beta‐adrenergic receptors subtypes In the rat aorta during development

The FASEB Journal (2012)

O.A. López-Canales Hilda Vargas‐Robles Mónica Griselda Arellano-Mendoza Jorge Skiold López‐Canales M.C. Castillo-Hernandez

During his life the rat shows changes in the relaxation response mediated by beta adrenergic receptors (βAR). In order to provide additional information on the topic, we studied the changes that may occur in the expression, localization and in vitro function of each subtype βAR in the thoracic aorta of male Wistar rats of two age groups: 3 weeks (prepuberty) and 9 weeks (postpuberty). The results indicate that, after the ninth week, the pretreatment with ICI 118.551 (β2 selective inhibitor, 10‐7 M) but not with CGP 12177 (selective inhibitor of β1, 10‐7 M) inhibited the relaxation response in all groups. However, the inhibition was greater when both antagonists were administered simultaneously. In addition, BRL 37344 (selective β3 agonist) caused relaxation only in prepuberty rats rings, which was blocked by SR 59230A (antagonist β3, 10‐6 M). Consistent with previous data, there was an increase in the expression of β1 and β2 receptors and decreased the β3 from the ninth week rats. Moreover, β1 and β2 subtypes are mainly located in smooth muscle, whereas β3 are located mainly in the endothelium. In conclusion, β1 receptors do not appear to participate functionally by themselves at any age, the β3 only involved in prepuberty rats and β2 are involved in all groups but their affinity is likely to change from the ninth week. Interestingly, the combination of β1 and β2 antagonists produced a synergistic effect which deserves further investigation.

Prepuberty

Adrenergic antagonist

10.1096/fasebj.26.1_supplement.674.6

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PP101—Reactivity modifications in heart resistance vessels to angiotensin II in isolated perfused heart of hypertensive rats

Clinical Therapeutics (2013)

M. Lopez-Calderon Lourdes Nallely Acevedo-Villavicencio Cleva Villanueva Eleazar Lara‐Padilla Gustavo Guevara‐Balcázar

High blood pressure (HBP) is a disease with high morbidity and mortality worldwide and is considered 1 of the main etiologic factors of multiple cardiac pathologies like cardiac hypertrophy, myocardial infarction, among others. One of the regulatory mechanisms of blood pressure is the renin angiotensin system (RAS), so much so that the first-line drugs in the treatment of hypertension are directed to some of the components of the RAS. However, these treatments frequently lead to the development of changes in morphology and physiology characterized by vascular complications .It is therefore necessary to consider adjuvant therapies to improve the outlook and quality of life of patients with HBP.

Hypertensive heart disease

Pathophysiology of hypertension

10.1016/j.clinthera.2013.07.130

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Efectos de la D-norpseudoefedrina sola y combinada con liotironina sobre la reactividad vascular en un vaso de conductancia y en el lecho vascular coronario de la rata

Revista del Hospital Juárez de México (2010)

Carlos Castillo‐Henkel Nadia Luz Guzmán-Lozano Jorge Skiold López‐Canales Gustavo Guevara‐Balcázar Juan Asbún‐Bojalil

Introduction. The D-norpseudoephedrine is an adrenergic amine with indirect action may be combined with liothyronine, aspect to consider in the risk-benefit analysis of drugs used in the treatment of obesity. Material and methods. The effect of Dnorpseudoephedrine on the aorta of male rats of the Wistar strain, under the protocol of the Bioethics Committee of the School of Medicine, Instituto Politecnico Nacional. The statistics were analyzed with ANOVA test. Results. The D-norpseudoephedrine induced a concentration-dependent contraction to well below the peak effect of phenylephrine. When the tone has been previously raised with phenylephrine, the D-norpseudoephedrine induces a concentration-dependent relaxation with a maximum effect of 25.07 ± 1.99% of reversion of the contractile effect induced by phenylephrine. Thyroid hormone did not alter the maximum effect of the D-norpseudoephedrine (0.1950 ± 0.01 vs. 0.1818 ± 0.01, in the absence and presence of liothyronine, respectively). Adrenergic amine caused a concentration-dependent increase in perfusion pressure with a lower maximum effect caused by phenylephrine (Emax 95.4 ± 12 and 39.2 ± 22.14 mmHg in the case of phenylephrine and D-norpseudoephedrine, respectively). Conclusions. The D-norpseudoephedrine causes contraction of the aorta at high concentrations (generally above Rev Hosp Jua Mex 2010; 77(3): 163-169 Castillo-Henkel C y cols. Reactividad vascular a D-norpseudoefedrina

Phenylephrine

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