Cardiovascular and renal manifestations of glutathione depletion induced by buthionine sulfoximine.
Oxidative stress contributes to the development of several cardiovascular diseases, including diabetes, renal insufficiency, and arterial hypertension. Animal studies have evidenced the association between higher blood pressure (BP) and increased oxidative stress, and treatment with antioxidants has been shown to reduce BP, while BP reduction due to antihypertensive drugs is associated with reduced oxidative stress. In 2000, it was first reported that oxidative stress and arterial hypertension were produced in normal Sprague-Dawley rats by oral administration of buthionine sulfoximine (BSO), which induces glutathione (GSH) depletion, indicating that oxidative stress may induce hypertension. The contribution of several potential pathogenic factors has been evaluated in the BSO rat model, the prototype of oxidative stress-induced hypertension, including vascular reactivity, endothelium-derived factors, renin-angiotensin system activity, TXA(2)-PGH(2) production, sodium sensitivity, renal dopamine-induced natriuresis, and sympathetic tone. This review summarizes the main factors implicated in the pathogenesis of BSO-induced hypertension and the alterations associated with GSH depletion that are related to renal function or BP control.
Departamento de Fisiología, Facultad de Medicina, Granada, Spain. fvargas@ugr.es
Félix
F
Vargas
Isabel
I
Rodríguez-Gómez
Rocío
R
Pérez-Abud
Pablo
P
Vargas Tendero
Yolanda
Y
Baca
Rosemary
R
Wangensteen
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019328:Buthionine Sulfoximine / Q000009:adverse effects / Q000494:pharmacology*; D002319:Cardiovascular System / Q000503:physiopathology*; D004195:Disease Models, Animal; D005978:Glutathione / Q000172:deficiency* / Q000187:drug effects / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D019328:Buthionine Sulfoximine; D005978:Glutathione