Chemogenetic Approaches to Probe Redox Pathways: Implications for Cardiovascular Pharmacology and Toxicology

Chemogenetics refers to experimental systems that dynamically regulate the activity of a recombinant protein by providing or withholding the protein's specific biochemical stimulus. Chemogenetic tools permit precise dynamic control of specific signaling molecules to delineate the roles of those molecules in physiology and disease. Yeast d-amino acid oxidase (DAAO) enables chemogenetic manipulation of intracellular redox balance by generating hydrogen peroxide only in the presence of d-amino acids. Advances in biosensors have allowed the precise quantitation of these signaling molecules. The combination of chemogenetic approaches with biosensor methodologies has opened up new lines of investigation, allowing the analysis of intracellular redox pathways that modulate physiological and pathological cell responses. We anticipate that newly developed transgenic chemogenetic models will permit dynamic modulation of cellular redox balance in diverse cells and tissues and will facilitate the identification and validation of novel therapeutic targets involved in both physiological redox pathways and pathological oxidative stress. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

First person – José Britto-Júnior

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. José Britto-Júnior is first author on ‘The basal release of endothelium-derived catecholamines regulates the contractions of Chelonoidis carbonaria aorta caused by electrical-field stimulation’, published in BiO. José conducted the research described in this article while a master's student in Professor Matheus L. Rocha's laboratory at Faculty of Pharmacy, University of Goias, and is now a PhD student in the Department of Pharmacology at the University of Campinas, Brasil, investigating basic cardiovascular pharmacology, endothelium, endothelial catecholamines and comparative physiology.

Integration of computer-simulated practical exercises into undergraduate medical pharmacology education at Mulungushi University, Zambia

Purpose: This study was conducted to determine whether a computer simulation of practical exercises in undergraduate medical pharmacology led to the realization of the intended learning outcomes.Methods: The study was a descriptive analysis of laboratory classes carried out using computer simulation programs. Five programs were used to teach practical pharmacology to undergraduate medical students at the Mulungushi University School of Medicine and Health Sciences. The study period was January 2018 to December 2019. The computer programs included a pharmacokinetics simulator (CyberPatient), organ bath simulator (OBSim), AutonomiCAL for simulating autonomic pharmacology, and Virtual Cat and Virtual Rat (RatCVS) for simulating cardiovascular pharmacology. Students utilized these programs during their pharmacology laboratory classes, wrote reports, and answered relevant clinical questions.Results: The 5 programs provided easy and precise platforms for students to explore concepts and demonstrate knowledge of pharmacokinetics, pharmacodynamics, autonomic and cardiovascular pharmacology, and their clinical applications.Conclusion: The programs were effective learning tools. Students’ learning was easily assessed based on their laboratory reports. Although the computer programs met medical students’ learning needs, wet laboratory exercises are also needed to meet the needs of students who require practical laboratory skills.

Neprilysin: A Potential Therapeutic Target of Arterial Hypertension?

Arterial hypertension is the most prevalent chronic disease in the adult population of developed countries and it constitutes a significant risk factor in the development of cardiovascular disease, contributing to the emergence of many comorbidities, among which heart failure excels, a clinical syndrome that nowadays represents a major health problem with uncountable hospitalizations and the indolent course of which progressively worsens until quality of life decreases and lastly death occurs prematurely. In the light of this growing menace, each day more efforts are invested in the field of cardiovascular pharmacology, searching for new therapeutic options that allow us to modulate the physiological systems that appear among these pathologies. Therefore, in the later years, the study of natriuretic peptides has become so relevant, which mediate beneficial effects at the cardiovascular level such as diuresis, natriuresis, and decreasing cardiac remodeling; their metabolism is mediated by neprilysin, a metalloproteinase, widely expressed in the human and capable of catalyzing many substrates. The modulation of these functions has been studied by decades, giving room to Sacubitril, the first neprilysin inhibitor, which in conjunction with an angiotensin receptor blocker has provided a high efficacy and tolerability among patients with heart failure, for whom it has already been approved and recommended. Nonetheless, in the matter of arterial hypertension, significant findings have arisen that demonstrate the potential role that it will play among the pharmacological alternatives in the upcoming years.