State-of-the-Art lecture. Role of angiotensin and oxidative stress in essential hypertension.
In this review, we examine the possibility that small increments in angiotensin II are responsible for an increase in blood pressure and maintenance of hypertension through the stimulation of oxidative stress. A low dose of angiotensin II (2 to 10 ng x kg(-1) x min(-1), which does not elicit an immediate pressor response), when given for 7 to 30 days by continuous intravenous infusion, can increase mean arterial pressure by 30 to 40 mm Hg. This slow pressor response to angiotensin is accompanied by the stimulation of oxidative stress, as measured by a significant increase in levels of 8-iso-prostaglandin F(2alpha) (F(2)-isoprostane). Superoxide radicals and nitric oxide can combine chemically to form peroxynitrite, which can then oxidize arachidonic acid to form F(2)-isoprostanes. F(2)-isoprostanes exert potent vasoconstrictor and antinatriuretic effects. Furthermore, angiotensin II can stimulate endothelin production, which also has been shown to stimulate oxidative stress. In this way, a reduction in the concentration of nitric oxide (which is quenched by superoxide) along with the formation of F(2)-isoprostanes and endothelin could potentiate the vasoconstrictor effects of angiotensin II. We hypothesize that these mechanisms, which underlie the development of the slow pressor response to angiotensin II, also participate in the production of hypertension when circulating angiotensin II levels appear normal, as occurs in many cases of essential and renovascular hypertension.
Romero
J C
JC
Department of Physiology and Biophysics, Mayo School of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Reckelhoff
J F
JF
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D015237:Dinoprost / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress
D000804:Angiotensin II; D009569:Nitric Oxide; D015237:Dinoprost