Category Archives: Cardiovascular


J Pharm Pharmacogn Res 2(Suppl. 1): S28, 2014

Special supplement with the abstract book of LATINFARMA 2013



Prozzi GR.

Applied Pharmacology, Faculty of Medicine, National University of La Plata. Health Institute, National University “Arturo Jauretche”. Argentina.

Introduction: The non-steroidal anti-inflammatory drugs (NSAIDs) are an important part of treatment for many people with painful and inflammatory conditions and are amongst the most commonly used drugs worldwide. The extent to which an NSAID inhibits the respective cyclooxygenase isoforms (COX-1 and COX-2) may be related to cardiovascular risk (CVR). There is a growing body of evidence that most NSAIDs are associated with an increased CVR, some more than others.

The aim was to review: the cardiovascular toxicity of different NSAIDs, epidemiology of use and recommendations of published guidelines.

Results: In the VIGOR (2000) study was observed that rofecoxib was associated with a fourfold increase in the incidence of myocardial infarction (MI) compared with naproxen. It was the first evidence of CVR of a coxib. Six years later, a meta-analysis of randomised trials, and a systematic review of the observational studies found that coxibs, diclofenac and possibly ibuprofen were associated with higher CVR than naproxen. Those were the first evidences of CVR of traditional NSAIDs. In 2011, a network meta-analyses of randomised trials, and the biggest systematic review of the observational studies reported similar results. The highest CVR were seen with coxibs and diclofenac and the lower with naproxen. In 2013, Bainget´s meta-analyses indicated that in high-dose, the CVR of diclofenac and possibly ibuprofen are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other. For every 1000 patients allocated to a year of treatment with a coxib regimen or high-dose diclofenac, about three would have a MI, of which one would be fatal. However, NSAIDs with a high CVR are still widely used. Diclofenac and etoricoxib together account for approximately one-third of all sales of NSAIDs in several countries.

Conclusions: While the benefits of NSAIDs for the treatment of pain outweighs their risks, their use should be at the lowest effective dose for the shortest possible time. Where pharmacological treatment is required for patients at risk of cardiovascular complications paracetamol, naproxen or aspirin is recommended and coxibs or diclofenac should be avoided.


J Pharm Pharmacogn Res 2(Suppl. 1): S1, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture


Moncada S.

The Wolfson Institute for Biomedical Research, University College London, United Kingdom.

In this lecture I will explain how the mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs were discovered and will also describe the discovery of prostacyclin and nitric oxide. I will discuss the biological relevance of those discoveries to our understanding of the physiology and pathophysiology of various organs and tissues and their implications for the therapy and prevention of different diseases. Finally I will consider the possibilities of future research in these areas of research.

Negative inotropic effect of naringin

J Pharm Pharmacogn Res 2(5): 148-157, 2014.

Original Article | Artículo Original

Mechanism of the negative inotropic effect of naringin in mouse heart

[Mecanismo del efecto inotrópico negativo de la naringina en el corazón de ratón]

Julio Alvarez-Collazoa, Ana I. López-Medinaa, Armando A. Rodríguezb, Julio L. Alvareza*

aLaboratorio de Electrofisiología. Instituto de Cardiología y Cirugía Cardiovascular. 17 N° 702, Vedado, La Habana, Cuba.bResearch Group for Experimental and Clinical Peptide Chemistry. Hannover Medical School, Hannover, Germany

Context: Naringin (NRG) is the major flavonoid (flavanone glycoside) in grapefruit juice. Its biological activity has been only partially characterized and little is known about the mechanism of the negative inotropic action of this flavonoid.

Aims: To evaluate the effects of NRG on the surface electrogram (ECG) and the force of contraction (FC) of mice hearts as well as on the sodium (INa), calcium (ICaL) and Na+ – Ca2+ exchange (INaCaX) currents of enzymatically isolated mouse ventricular cardiomyocytes.

Methods: ECG and FC were recorded on mouse hearts perfused in a Langendorff column. Ventricular cardiomyocytes were enzimatically dissociated and ionic currents recorded with the patch-clamp technique.

Results: NRG increased RR interval and shortened corrected QT only at high concentrations (30-100 µM). However, at a fixed heart rate, it decreased FC with an IC50 of 0.4 µM. NRG reduced INa with an IC50 of 0.07 µM but with a maximal inhibition of 60 %. NRG also depressed ICaL with an IC50 of 0.013 µM and increased its fast inactivation time constant. The effects on ICaL were not voltage-dependent. INaCaX was not affected by NRG.

Conclusions: Our results indicate that NRG exerts a negative inotropic effect in mice hearts that could be explained by a decrease in INa and ICaL. These actions should be taken into account when considering this molecule either as a dietetic supplement or as a template to develop therapeutic agents for human diseases.

Keywords: Calcium; cardiac; flavonoids; naringenin, naringin; sodium.


Contexto: La naringina (NRG) es el principal flavonoide (glicósido de flavanona) en el jugo de toronja. Su actividad biológica ha sido solo parcialmente caracterizada y poco se conoce acerca del mecanismo de la acción inotrópica negativa de este flavonoide.

Objetivos: Evaluar los efectos de la NRG sobre el electrograma de superficie (ECG) y la fuerza de contracción (FC) de corazones de ratón, así como sobre las corrientes de sodio (INa), calcio (ICaL) y del intercambiador Na+ – Ca2+ (INaCaX) en cardiomiocitos ventriculares de ratón, aislados enzimáticamente.

Métodos: El ECG y la FC se registraron en corazones de ratón perfundidos en una columna de Langendorff. Los cardiomiocitos ventriculares se disociaron enzimáticamente y las corrientes iónicas se registraron con la técnica de patch-clamp.

Resultados: La NRG incrementó el intervalo RR intervalo y acortó el QT solo a altas concentraciones (30-100 µM). No obstante, a frecuencia cardíaca fija, disminuyó la FC con un IC50 de 0.4 µM. La NRG redujo INa con un IC50 de 0.07 µM pero con una máxima inhibición de 60 %. La NRG también redujo ICaL con un IC50 de 0.013 µM e incrementó su constante de inactivación rápida. Los efectos sobre ICaL no fueron dependientes del potencial. La INaCaX no fue afectada por la NRG.

Conclusiones: Nuestros resultados indican que la NRG ejerce un efecto inotrópico negativo en corazones de ratón que puede ser explicado por una reducción en INa e ICaL. Esas acciones deben ser tomadas en cuenta al considerar a esta molécula como suplemento dietético o como plantilla para desarrollar nuevos agentes terapéuticos para tratar las enfermedades en humanos.

Palabras Clave: Calcio; cardíaco; flavonoides; naringenina; naringina; sodio.

Download the PDF file .

Citation Format: Alvarez-Collazo J, López-Medina AI, Rodríguez AA, Alvarez JL (2014) Mechanism of the negative inotropic effect of naringin in mouse heart. J Pharm Pharmacogn Res 2(5): 148-157.
This article has been cited by:
Galán-Martínez L, Herrera-Estrada I, Fleites-Vázquez A (2018) Direct actions of the flavonoids naringenin, quercetin and genistein on rat cardiac and vascular muscles. J Pharm Pharmacogn Res 6(3): 158–166. Website
Ait-Oubahou A, Benichou M, Sagar M, Kaanane A, Yahia EM (2017) Citrus, In Fruit and Vegetable Phytochemicals: Chemistry and Human Health, 2nd Edition (ed E. M. Yahia), Chichester, UK: John Wiley & Sons, Ltd. DOI: 10.1002/9781119158042.ch49

© 2014 Journal of Pharmacy & Pharmacognosy Research (JPPRes)