Reactive Oxygen Species Mediates Vasoconstriction Induced By Angiotensin Ⅱ In Spontaneously Hypertensive Rats

Hypertension is the common and severe cardiovascular disease of human being. It is mainly characterized by persistent increase of peripheral vascular resistance which causes the increase of blood pressure and is often accompanied by structural changes of heart and blood vessels. In hypertension, angiotensinâ…¡(Angâ…¡) induces an elevated expression of the AT1 receptors in endothelial cells and smooth muscle cells, and enhances the sensitivity to some vasoconstrictive substances. Angâ…¡plays an important role in the development of hypertension and its complication. Previous studies suggested that reactive oxygen species (ROS) in the paraventricular nucleus mediated the enhancement of cardiac sympathetic afferent reflex, the increase of renal sympathetic nerve activity and blood pressure induced by Angâ…¡. However, it is not clear whether the ROS mediates the vasoconstriction caused by Angâ…¡. In the present study, we investigated the role of ROS in the vasoconstriction caused by Angâ…¡and the origin of ROS. Furthermore, whether the effect of ROS on the vasoconstrictor responses evoked by Ang II denpends on the intact of the endothelial cells were determined. These studies lay a foundation and provide clues for finding new antihypertension drugs.The study was carried out on the isolated arterial rings perfusion model in thoracic aorta and mesenteric arteries in SHR and nomotensive Wistar rats. Vascular reactivity to vasoactive substances was evaluated by the change of tension in thoracic aorta and mesenteric arteries. The primary findings were as follows: 1. Angâ…¡dose-dependently increased the tension in both endothelium-intact and endothelium-denuded thoracic aortic rings and mesenteric arteries of Wistar and SHR. Compared with Wistar rats, it had more significant vasoconstriction responses evoked by the same dose of Angâ…¡in SHR. Compared with the artery rings with intact endothelium, the endothelium-denuded rings had more significant changes in vessel tension.2. Superoxide anion scavenger tempol reduced the basal tone of artery rings with intact endothelium of SHR. Superoxide dismutase(SOD) inhibitor DETC enhanced the tension of artery rings with intact endothelium in both Wistar and SHR; Tempol and DETC had no significant effect on the endothelium-denuded artery rings of Wistar and SHR.3. Pretreatment with superoxide anion scavenger tempol had no significant effect on the vasoconstriction responses evoked by Ang II in endothelium-intact artery rings of SHR and Wistar. It had no significant effect on the vasoconstriction response evoked by Ang II in artery rings with intact endothelium of Wistar, but it significantly reduced the vasoconstriction responses evoked by Ang II in endothelium-intact artery rings of SHR. SOD inhibitor DETC had no significant effect on the vasoconstrictor response evoked by Ang II in endothelium-denuded artery rings of SHR and Wistar. It had no significant effect on the vasoconstrictor responses evoked by Ang II in endothelium-intact artery rings of Wistar, but significantly enhanced the vasoconstrictor responses evoked by Ang II in endothelium-intact artery rings of SHR.4. NADPH oxidase inhibitor apocynin significantly reduced the tension of the rings with intact endothelium of SHR, but it had no significant effect on the tone of rings with intact endothelium of Wistar. Apocynin had no significant effect on the rings without endothelium of Wistar and SHR.5. Pretreatment with NADPH oxidase inhibitor apocynin had no significant effect on the vasoconstrictor responses evoked by Ang II in artery rings without endothelium of Wistar and SHR, but significantly reduced the vasoconstriction responses evoked by Ang II in artery rings with endothelium of Wistar and SHR.6. Nitricoxide synthase inhibitor L-NAME slightly enhanced the basal tone of rings in Wistar and SHR, and SHR was more sensitive to L-NAME.7. Pretreatment with nitricoxide synthase inhibitor L-NAME had no significant effect on the vasoconstriction responses evoked by Ang II in endothelium-denuded aortic rings of Wistar and SHR, but it significantly enhanced the vasoconstrictor responses evoked by Ang II on the artery rings with endothelium of Wistar and SHR.The results show that ROS in the thoracic aorta and mesenteric artery increases the vessel tension of SHR and mediates the vasoconstrictor responses evoked by Ang II, which denpendes on the integrity of endothelium; NADPH oxidase is the main origin of ROS; NO inhibits the vasoconstriction responses evoked by Ang II of artery rings with intact endothelium of Wistar and SHR.