Vascular oxidative stress, NF¿B activation and AT1 Receptor upregulation precede the development of hypertension in Spontaneously Hypertensive Rats (SHR)

Abstract

Oxidative stress is strongly associated to hypertension. However, it is unclear whether oxidative stress is a cause or a consequence of hypertension and what role it plays in this disease. A hallmark of hypertension is abnormal vascular tone which is, in part, due to Angiotensin II type I receptor (AT1R) upregulation, the cause of which is unknown. We have previously shown that oxidative stress activates NF¿B, a redox sensitive transcription factor, via nuclear translocation which contributes to AT1R upregulation and subsequent hypertension. Here we report that vascular oxidative stress, NF¿B activation and AT1R upregulation precede the development of hypertension in SHR. The blood pressure in young SHR (3‐4 wk old) was similar to the age‐matched normotensive Wistar Kyoto rats (WKY). These SHR exhibited vascular oxidative stress as evidenced by increased oxidized glutathione levels, protein carbonylation and decreased superoxide dismutase activity as compared to WKY. The SHR vasculature also showed increased nuclear levels of NF¿B p65 subunit and increased AT1R protein levels. In conclusion, vascular oxidative stress via NF¿B activation may induce AT1R upregulation which precedes development of hypertension. This early evidence of oxidative stress suggests that it might be a cause of hypertension and may play a pivotal role in hypertension development by causing AT1R upregulationGrant AHA SDG 0835428N