Dr Carolyn Lam: Welcome to Circulation On The Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley: And I'm Greg Hundley, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. But I am running to hide today, because I am going to get quizzed by the master in the feature discussion. And listeners, it's really interesting. It involves quantitative myocardial perfusion using magnetic resonance imaging, but also adding the twist that artificial intelligence computer algorithms are being used to read the stress test images without any physician interference. Oh, my goodness. I don't know what she's going to quiz me about. Dr Carolyn Lam: Absolutely about all the AI algorithms and exactly how you derive them. But why don't you tell us what you want to describe first and the rest of the issue. Dr Greg Hundley: Carolyn, I'm going to start with a paper on peroxynitrite and as you know, that's a very short-lived free radical produced in cells, part of the both oxidative and nitrosative stress pathways. And this article comes from Dr Swapnil Sonkusare from the University of Virginia School of Medicine. Well, Carolyn, this study is involving mouse models, and the investigators evaluated the relationship between peroxynitrite, that powerful oxidative nitrosative stress molecule, and obesity and hypertension. Dr Carolyn Lam: Nice. And before you ask me anything more about peroxynitrite, because I think you just summarize everything I know. What did the authors find, Greg? Dr Greg Hundley: What that found is that obesity induced impairment of endothelial AKAP150-TRPV4 channel signaling contributes to the loss of endothelial function and elevated blood pressure. And lowering the levels of this oxidant molecule of peroxynitrite reduces endothelial AKAP150-TRPV4 channel signaling, vasodilation and blood pressure and obesity. Dr Carolyn Lam: And what are the implications? Dr Greg Hundley: Well, endothelial TRPV4 channels are essential regulators of resting blood pressure and impairment of endothelial TRPV4 channel activity contributes to obesity induced hypertension. And therefore, therapeutic strategies, perhaps in the future, that lower peroxynitrite levels can be used to rescue endothelial TRPV4 channel activity, endothelial function and blood pressure in obese individuals. Dr Carolyn Lam: Nice, Greg. Well, I want to tell you a little bit more about plain old hypertension. Now, we know that blood pressure is regulated by the function of the kidney vasculature and sympathetic nervous system, but do immune cells play a role? Well, Dr Guzik from University Medical College, Krakow, Poland, and University of Glasgow and his colleagues, studied the relationship between major white blood cell types and blood pressure in the UK Biobank population and employed a Mendelian randomization analysis to examine which leukocyte populations maybe causally linked to blood pressure. Dr Greg Hundley: So we've got another blood pressure article. What did they find? Dr Carolyn Lam: They found potentially causal positive effects of total blood lymphocyte count with blood pressure. Among the mechanisms that might mediate this relationship, they found evidence that blood lymphocyte count might influence albuminuria. The study may additionally support a reverse, potentially causal positive effect of blood pressure indices on blood neutrophil monocyte and you sit a full count. So fairly interesting. Dr Greg Hundley: Very nice. So I'm going to switch over and talk a little bit about lifestyle interventions. I know you're a big fitness buff. So this paper is about fitness, body mass index and the risk of heart failure in overweight, obese individuals with type two diabetes mellitus. It's an analysis from The Look AHEAD Trial. The corresponding author is Dr Ambarish Pandey from the University of Te