Data concerning the effects of cannabidiol (CBD) on blood pressure (BP) is controversial. HYPER-H21-4 was a randomized, placebo-controlled, crossover trial which sought to elucidate if 5-week administration of CBD will reduce BP in hypertensive patients. In the substudy of this trial, we aimed to establish the mechanistic background of CBD-induced BP reduction. Specifically, we explored the dynamic of catestatin, a sympathoinhibitory peptide implicated in the pathophysiology of hypertension. In the present analysis, 54 patients with Grade 1 hypertension were included. 5-week administration of CBD but not placebo reduced serum catestatin concentration in comparison to baseline (13.50 [10.85-19.05] vs. 9.65 [6.37-12.26] ng/mL, p < 0.001). Serum catestatin levels at the start of the treatment period demonstrated a negative correlation with the extent of reduction in mean arterial pressure (r = -0.474, p < 0.001). Moreover, the extent of change in catestatin serum levels showed a strong correlation with the extent of mean arterial pressure reduction (r = 0.712, p < 0.001). Overall, the results of the present study imply that the antihypertensive effects of CBD may be explained by its interaction with the sympatho-chromaffin system, although further research is warranted.

We studied the expression of connexin 43 (Cx43) and pannexin 1 (PANX1) in different cellular populations of the kidneys of diabetic mice and diabetic and non-diabetic patients, to evaluate their role as potential therapeutic targets in diabetic kidney disease (DKD). A combination of a low dose of streptozotocin and a high-fat diet (HFD) was used to induce a type 2 diabetes model (DM2) in mice. Kidney tissues from diabetic (n = 9) and control patients (n = 11) who underwent nephrectomy were collected. Tissues from mice and humans were processed for double immunofluorescence, using antibodies against Cx43, phosphorylated Cx43 (pCx43) or PANX1 and markers for specific cell populations: endothelium (CD31/PECAM1); pericytes/mesangium (PDGFRB); podocytes (nephrin/synaptopodin); proximal tubules and collecting ducts (aquaporin 2). The results showed a significant decrease in the expression of pCx43 in PDGFRB-immunoreactive mesangium in diabetic patients compared to the control group (p < 0.0001). This contrasted with an increase in pCx43 in pericytes of diabetic mice (p = 0.1). However, we found a general decrease in Cx43 protein expression in diabetic mouse kidneys (p < 0.05). We also found a decrease in the expression of PANX1 in endothelial cells of diabetic patients (p < 0.05) and a significant increase in PANX1 expression in cells expressing PDGFRB (p < 0.05). Expression of PANX1 in endothelium (r = −0.50; p < 0.05) and pCx43 in the mesangium (r = −0.65; p < 0.01) correlated negatively with the percentage of sclerotic glomeruli. The expression and activation of Cx43 and the expression of PANX1 are altered in distinct populations of renal cells during long-term type 2 diabetes mellitus, especially cells of the vascular wall. This may indicate their role in the pathophysiological processes of DKD. Therefore, connexin and pannexin channels could be considered as possible therapeutic targets in the prevention and treatment of diabetic kidney disease.