Phenylephrine stimulates the production of reactive oxygen species (ROS) in endothelial cells from hypertensive but not in normotensive rat aorta

Abstract

The endothelial cells (EC) play important role in the vascular tone control. The production of ROS is increased in hypertension that can modify the contractile response to agonists. This study aimed to evaluate the role of EC on the phenylephrine (PE)‐induced contraction in normotensive (2K) and renal hypertensive (2K‐1C) rat aorta and the effect of PE on the production of ROS in EC from both rat groups. Concentration‐effect curves were constructed for PE in 2K and 2K‐1C intact endothelium (E+) or denuded aortas (E−). The efficacy (Emax) and potency (pD2) were compared. Isolated EC were incubated with the ROS‐sensitive dye DHE and the fluorescence intensity (FI) was measured by flow citometry. EC were stimulated with PE (0.1μM) for 10 min with the antioxidants superoxide scavenger Tiron or Catalase. The contraction was similar in 2K and 2K‐1C E− aortas. In E+ aortas the Emax was lower in 2K‐1C rings (1.2±0.2g, n=7 p<0.001) than in 2K (2.2±0.1g, n=5), but the potency was not different between them. Basal FI of DHE on EC was similar in 2K (43388.5±869.8, n=4) and 2K‐1C (37373.0±536.2, n=4), which was increased by PE only in 2K‐1C (68911.5±4146.3, n=4 p<0.001). The enhancement of ROS was reversed to the basal levels by the antioxidants. Our results suggest that the lower contraction induced by PE in intact endothelium 2K‐1C aorta can be due to the EC increased production of ROS stimulated by PE.Supported by FAPESP, CAPES and CNPq.