Activation of the aryl hydrocarbon receptor (AhR) has been shown to be important in physiological processes other than detoxification, including vascular homeostasis. Although AhR is highly expressed in the endothelium, its function has been poorly studied. This systematic review aims to summarise current knowledge on the AhR role in the endothelium and its cardiovascular implications. We focus on endogenous AhR agonists, such as some uremic toxins and other agonists unrelated to environmental pollutants, as well as studies using AhR knockout models. We conclude that AhR activation leads to vascular oxidative stress and endothelial dysfunction and that blocking AhR signalling could provide a new target for the treatment of vascular disorders such as cardiovascular complications in patients with chronic kidney disease or pulmonary arterial hypertension.

Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient’s life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible. However, reperfusion activates several cellular cascades that contribute to organ dysfunction, resulting in the ischaemia/reperfusion (I/R) injury. The search for treatments against AMI and I/R injury is urgent due to the shortage of effective treatments at present. In this regard, histone deacetylase (HDAC) inhibitors emerge as a promising treatment against myocardial infarction. The objective of this systematic review is to analyse the effects of HDAC inhibitors on ventricular function, cardiac remodelling and infarct size, among other parameters, focusing on the signalling pathways that may mediate these cardiovascular effects and protect against AMI. Methods: Original experimental studies examining the effects of HDAC inhibitors on AMI were included in the review using the PubMed and Scopus databases. Non-experimental papers were excluded. The SYRCLE RoB tool was used to assess risk of bias and the results were summarised in a table and presented in sections according to the type of HDAC inhibitor used. Results: A total of 18 studies were included, 10 of them using trichostatin A (TSA) as an HDAC inhibitor and concluding that the treatment improved ventricular function, reduced infarct size, and inhibited myocardial hypertrophy and remodelling after AMI. Other HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), mocetinostat, givinostat, entinostat, apicidin, and RGFP966, were also analysed, showing antioxidant and anti-inflammatory effects, an improvement in cardiac function and remodelling, and a decrease in apoptosis, among other effects. Conclusions: HDAC inhibitors constitute a significant promise for the treatment of AMI due to their diverse cardioprotective effects. However, high risk of selection, performance, and detection bias in the in vivo studies means that their application in the clinical setting is still a long way off and more research is needed to better understand their benefits and possible side effects.

T‐type voltage‐gated calcium channels (VGCCs) are comparatively understudied in large conduit artery function relative to the well‐characterized L‐type channel subtype. This study investigates the vascular roles of T‐type VGCCs in the aorta and renal artery of healthy rabbits using functional reactivity assays and immunofluorescence and further elucidates the interaction between T‐type VGCC activity and the nitric oxide (NO) signalling pathway. T‐type VGCCs contributed to contractile responses induced by phenylephrine and angiotensin II in both arteries. Moreover, in the renal artery, the contribution of T‐type VGCCs in response to phenylephrine increased in the absence of NO and was associated with endothelium‐dependent vasodilation. Immunofluorescence analysis revealed co‐localization of Ca _V 3.1 with endothelial nitric oxide synthase in the renal artery, but not in the aorta, suggesting a vasodilatory role in renal circulation. These findings highlight vascular bed‐specific functions of T‐type VGCCs and their interaction with endothelial pathways in the renal artery.

Sympathetic nervous system (SNS), endothelin 1 (ET-1) and angiotensin II (Ang II) are involved in the pathophysiology of acute myocardial infarction (AMI). Valproic acid (VPA) is under study for the treatment against AMI due to its beneficial cardiac effects. However, the vascular effects of VPA on the activation of the SNS, ET-1 and Ang II after AMI are not fully studied. In our study, we used aorta from New Zealand White rabbits without AMI, with AMI and AMI treated with VPA (500 mg/kg/day). AMI was induced by occluding the left circumflex coronary artery for 1 h, followed by reperfusion. After 5 weeks, we studied the ex vivo vascular reactivity in organ bath and measured protein expression by Western blot. Our findings indicated that AMI increased vasoconstriction to exogenous and endogenous NE and ET-1, which was reversed by VPA eliciting upregulation of α₂-adrenergic and ETB receptors and downregulating ETA receptors. Although no changes in the vascular response to Ang II were observed in AMI or VPA-treated rabbits, an increase in Ang II type 2 receptor expression was found in VPA-treated rabbits. We conclude that VPA could be considered a vascular protector by modulating SNS, ET-1 and Ang II in the aorta, which together with its cardioprotective effect would make it a promising candidate for the treatment of AMI.