Beneficial Consequences of One-Month Oral Treatment with Cannabis Oil on Cardiac Hypertrophy and the Mitochondrial Pool in Spontaneously Hypertensive Rats.

It has been demonstrated the dysregulation of the cardiac endocannabinoid system in cardiovascular diseases. Thus, the modulation of this system through the administration of phytocannabinoids present in medicinal cannabis oil (CO) emerges as a promising therapeutic approach. Furthermore, phytocannabinoids exhibit potent antioxidant properties, making them highly desirable in the treatment of cardiac pathologies, such as hypertension-induced cardiac hypertrophy (CH).

New advances in the protective mechanisms of acidic pH after ischemia: Participation of NO.

Background: It has been previously demonstrated that the maintenance of ischemic acidic pH or the delay of intracellular pH recovery at the onset of reperfusion decreases ischemic-induced cardiomyocyte death.

Objective: To examine the role played by nitric oxide synthase (NOS)/NO-dependent pathways in the effects of acidic reperfusion in a regional ischemia model.

Methods: Isolated rat hearts perfused by Langendorff technique were submitted to 40 min of left coronary artery occlusion followed by 60 min of reperfusion (IC).

Is N-methylacetazolamide a possible new therapy against ischemia-reperfusion injury?

The increase of intracellular Ca concentration, produced principally by its influx through the L-type Ca channels, is one of the major contributors to the ischemia-reperfusion injury. The inhibition of those channels in different experimental models was effective to ameliorate the post-ischemic damage. However, at a clinical level, the results were contradictory.

Cardioprotective effects of N-methylacetazolamide mediated by inhibition of L-type Ca channel current.

Our objective was to examine the effects of N-methylacetazolamide (NMA), a non‑carbonic anhydrase inhibitor, on ischemia-reperfusion injury. Isolated rat hearts were assigned to the following groups: 1) Non-ischemic control (NIC):110 min of perfusion and 2) Ischemic control (IC): 30 min of global ischemia and 60 min of reperfusion (R). Both groups were repeated in presence of NMA (5 μM), administered during the first 10 min of R.

Myocardial and mitochondrial effects of the anhydrase carbonic inhibitor ethoxzolamide in ischemia-reperfusion.

We have previously demonstrated that inhibition of extracellularly oriented carbonic anhydrase (CA) isoforms protects the myocardium against ischemia-reperfusion injury. In this study, our aim was to assess the possible further contribution of CA intracellular isoforms examining the actions of the highly diffusible cell membrane permeant inhibitor of CA, ethoxzolamide (ETZ). Isolated rat hearts, after 20 min of stabilization, were assigned to the following groups: (1) Nonischemic control: 90 min of perfusion; (2) Ischemic control: 30 min of global ischemia and 60 min of reperfusion (R); and (3) ETZ: ETZ at a concentration of 100 μM was administered for 10 min before the onset of ischemia and then during the first 10 min of reperfusion.

Isoespintanol, a monoterpene isolated from oxandra cf xylopioides, ameliorates the myocardial ischemia-reperfusion injury by AKT/PKCε/eNOS-dependent pathways.

Purpose: To determine the actions of isoespintanol (Isoesp) on post-ischemic myocardial and mitochondrial alterations.

Methods: Hearts removed from Wistar rats were perfused by 20 min. After this period, the coronary flow was interrupted by half an hour and re-established during 1 h.

Calcineurin/P38MAPK/HSP27-dependent pathways are involved in the attenuation of postischemic mitochondrial injury afforded by sodium bicarbonate co-transporter (NBCe1) inhibition.

The electrogenic sodium bicarbonate co-transporter isoform 1 (NBCe1) plays an important role in ischemia-reperfusion injury. The cardioprotective action of an antibody directed to the extracellular loop 3 (a-L3) of NBCe1 was previously demonstrated by us. However, the role of a-L3 on mitochondrial post-ischemic alterations has not yet been determined.

Cardioprotection and natural polyphenols: an update of clinical and experimental studies.

Myocardial ischemia is the leading cause of death worldwide. Despite better outcomes with early coronary artery reperfusion strategies, morbidity and mortality remain significant. The principal myocardial hallmark of myocardial ischemia is cell death and the associated impairment of cardiac contractility.

Cardioprotection of benzolamide in a regional ischemia model: Role of eNOS/NO.

Background: Recent studies from our laboratory show the cardioprotective action of benzolamide (BZ, carbonic anhydrase inhibitor) against ischemia-reperfusion injury. However, the mechanisms involved have not been fully elucidated.

Objective: To examine the participation of the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) in the effects of BZ in a model of regional ischemia.

Survival kinase-dependent pathways contribute to gender difference in the response to myocardial ischemia-reperfusion and ischemic post-conditioning.

The response to ischemia/reperfusion and the effects of ischemic post-conditioning (IPC) are sex-dependent, but the mechanisms have not been clarified. Male (M) and female (F) rat hearts isolated and perfused using the Langendorff technique were subject to 30 min of global ischemia (GI) and 60 min reperfusion (R). In IPC hearts, three cycles of 30-sec GI/30-sec R were applied at the beginning of R.

Benzolamide perpetuates acidic conditions during reperfusion and reduces myocardial ischemia-reperfusion injury.

During ischemia, increased anaerobic glycolysis results in intracellular acidosis. Activation of alkalinizing transport mechanisms associated with carbonic anhydrases (CAs) leads to myocardial intracellular Ca increase. We characterize the effects of inhibition of CA with benzolamide (BZ) during cardiac ischemia-reperfusion (I/R).

Ex Vivo Treatment with a Polyphenol-Enriched Cocoa Extract Ameliorates Myocardial Infarct and Postischemic Mitochondrial Injury in Normotensive and Hypertensive Rats.

Our objective was to determine the effects of a polyphenol-enriched cocoa extract (PCE) on myocardial postischemic alterations in normotensive (Wistar rats, W) and spontaneously hypertensive rats (SHR). Isolated hearts were submitted to 110 min of perfusion or 20 min stabilization, 30 min global ischemia, and 60 min reperfusion (R). Other hearts were treated with PCE at the onset of R.

Data supporting the cardiac mitochondria calcium handling in female normotensive and spontaneously hypertensive rats.

In association with the published article "Mitochondrial calcium handling in normotensive and spontaneously hypertensive rats: correlation with systolic blood pressure levels" [1], this data article contains information about calcium handling of cardiac mitochondria isolated from female of both rats strains (WKY and SHR). Dataset of mitochondrial permeability transition pore (mPTP) resistance to opening Ca(2+)-mediated, Ca(2+) retention capacity (CRC), time constants and mitochondrial membrane potential (ΔΨm) are showed.

Cyclosporine-A mimicked the ischemic pre- and postconditioning-mediated cardioprotection in hypertensive rats: Role of PKCε.

Our aim was to assess the action of cyclosporine-A (CsA) against reperfusion injury in spontaneously hypertensive rats (SHR) compared to the effects of ischemic pre- (IP) and postconditioning (IPC), examining the role played by PKCε. Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1h reperfusion (R); IP: a cycle of 5 min GI and 10 min of R prior to 45 min-GI; and IPC: three cycles of 30s-GI/30s-R at the start of R. Other hearts of the IC, IP and IPC groups received CsA (mitochondrial permeability transition pore inhibitor) or chelerythrine (Che, non-selective PKC inhibitor).

Effect of an Ilex paraguariensis (yerba mate) extract on infarct size in isolated rat hearts: the mechanisms involved.

Tea made from Ilex paraguariensis (IP) dried and minced leaves is a beverage widely consumed by large populations in South America as a source of caffeine (stimulant action) and for its medicinal properties. However, there is little information about the action of IP on the myocardium in the ischemia-reperfusion condition. Therefore, the objective of this study was to examine the effects of an aqueous extract of IP on infarct size in a model of regional ischemia.

Mitochondrial calcium handling in normotensive and spontaneously hypertensive rats: correlation with systolic blood pressure levels.

The aim was to study the mitochondrial Ca(2+) handling of mitochondria isolated from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) hearts and to establish a possible correlation with systolic blood pressure (SBP). Mitochondrial swelling after Ca(2+) addition, Ca(2+)-retention capacity (CRC) by calcium green method, and membrane potential (ΔΨm) were assessed. SBP was 124±1 (WKY) and 235±6mmHg (SHR).

Cardioprotective efficacy against reperfusion injury of EMD-87580: Comparison to ischemic postconditioning.

Previous results show that prolonged treatment with EMD-87580 (EMD) NHE-1 blocker attenuates and reverses postinfarction remodelling. Our aim was to evaluate the effects of the treatment of EMD compared to ischemic postconditioning (IPO) in a model of regional ischemia. Isolated hearts were subjected to 40-min coronary occlusion followed by 60-min reperfusion (IC).

The electrogenic cardiac sodium bicarbonate co-transporter (NBCe1) contributes to the reperfusion injury.

Background: Although the participation of the electrogenic sodium/bicarbonate cotransporter (NBCe1) in the recovery from an intracellular acid load is recognized, its role in ischemia-reperfusion is still unclear.

Methods And Results: Our objective was to assess the role of NBCe1 in reperfusion injury. We use selective functional antibodies against extracellular loop 3 (a-L3) and loop 4 (a-L4) of NBCe1.

Gsk-3β inhibitors mimic the cardioprotection mediated by ischemic pre- and postconditioning in hypertensive rats.

The aim of this study was to examine the effects of GSK-3 β inhibitors compared with PRE and POS in spontaneously hypertensive rats (SHR). Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1-hour reperfusion (R); PRE: a cycle of 5 min GI and 10 minutes of R prior to 45 min GI; POS: three cycles of 30 sec GI/30 sec R at the start of R. Other hearts received lithium chloride (LiCl) or indirubin-3'-monoxime,5-iodo-(IMI) as GSK-3 β inhibitors.

Protective effects of N-(2-mercaptopropionyl)-glycine against ischemia-reperfusion injury in hypertrophied hearts.

The beneficial effects of N-(2-mercaptopropionyl)-glycine (MPG) against ischemia-reperfusion injury in normotensive animals have been previously studied. Our objective was to test the action of MPG during ischemia and reperfusion in hearts from spontaneously hypertensive rats (SHR). Isolated hearts from SHR and age-matched normotensive rats Wistar Kyoto (WKY) were subjected to 50-min global ischemia (GI) and 2-hour reperfusion (R).

Participation of mitochondrial permeability transition pore in the effects of ischemic preconditioning in hypertrophied hearts: role of NO and mitoKATP.

Background: The mitochondrial permeability transition pore (mPTP) plays an important role in ischemia-reperfusion in normotensive animals. Our study aims to define their participation in the ischemic preconditioning (IP) in hypertrophied hearts and to assess the role played by NO and mitochondrial ATP-dependent K channels (mitoKATP).

Material And Methods: Isolated hearts from spontaneously hypertensive rats (SHR) and age-matched normotensive rats Wistar Kyoto (WKY) were subjected to 35-min or 50-min global ischemia (GI) followed by 2-hour reperfusion (R).

In vivo key role of reactive oxygen species and NHE-1 activation in determining excessive cardiac hypertrophy.

Growing in vitro evidence suggests NHE-1, a known target for reactive oxygen species (ROS), as a key mediator in cardiac hypertrophy (CH). Moreover, NHE-1 inhibition was shown effective in preventing CH and failure; so has been the case for AT1 receptor (AT1R) blockers. Previous experiments indicate that myocardial stretch promotes angiotensin II release and post-translational NHE-1 activation; however, in vivo data supporting this mechanism and its long-term consequences are scanty.

Mitochondrial KATP channels participate in the limitation of infarct size by cariporide.

The objective of this study is to assess the participation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels in the cardioprotective effects of the Na(+)/H(+) exchanger (NHE-1) blocker cariporide in isolated rat hearts. Regional ischemia was induced by occlusion of left anterior descending coronary artery during 40 min followed by 2-h reperfusion (IC). Cariporide (C, 10 μΜ), or C plus 5-hydroxydecanoate (5-HD, 100 μM, a selective mitoK(ATP) channel inhibitor), or C plus chelerythrine (Chele, 1 μM, a PKC inhibitor), or an opener of mitoK(ATP) channels, diazoxide (Dz, 100 μM) was applied at the onset of reperfusion.

Myocardial reperfusion injury: reactive oxygen species vs. NHE-1 reactivation.

Background/aims: Flow restoration to ischemic myocardium reduces infarct size (IS), but it also promotes reperfusion injury. A burst of reactive oxygen species (ROS) and/or NHE-1 reactivation were proposed to explain this injury. Our study was aimed to shed light on this unresolved issue.

Is cardiac hypertrophy in spontaneously hypertensive rats the cause or the consequence of oxidative stress?

The aim of this work was to assess the possible correlation between oxidative damage and the development of cardiac hypertrophy in heart tissue from young (40-d-old) and older (4-, 11- and 19-month-old) spontaneously hypertensive rats (SHR) in comparison with age-matched Wistar (W) rats. To this end, levels of thiobarbituric acid reactive substances (TBARS), nitrotyrosine contents, NAD(P)H oxidase activity, superoxide production, and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were determined. Compared to age-matched normotensive rats, SHR showed a significant increase in systolic blood pressure from 40 d of age and left ventricular hypertrophy (LVH) was significantly evident from 4 months of age.