Targeting reactive oxygen species in hypertension.
OBJECTIVE
Hypertension is a major risk factor for vascular diseases such as stroke, myocardial infarction, and renal microvascular disease. The mechanism by which vascular disease develops is complex, and growing evidence suggests that an increase in reactive oxygen species during hypertension is a major contributing factor. NADPH oxidase, the primary source of reactive oxygen species in the cardiovascular system, is a strong candidate for the development of therapeutic agents to ameliorate hypertension and end-organ damage.


RESULTS
Various scavengers and inhibitors of reactive oxygen species have been proposed for use in animal as well as human studies. While many of these agents are effective at lowering tissue reactive oxygen species levels, their specificity is a serious concern. Our laboratory has developed cell-permeant peptidic inhibitors targeting key interactions among the different NAD(P)H oxidase homologues. One of these inhibitors targeting nox2 and p47-phox interaction has proven useful in attenuating target neoplasia and hypertrophy.


CONCLUSIONS
Strategies aimed at specifically inhibiting NAD(P)H oxidase have proven effective in attenuating cardiovascular oxidative stress. The development of new inhibitors targeting novel oxidase homologues appears to hold significant promise for clarifying the physiologic role of these homologues as well as for the development of new antioxidant therapies.
Hypertension and Vascular Research Division, Henry Ford Health System, Detroit, Michigan 48202, USA.
M Eugenia
ME
Cifuentes
Patrick J
PJ
Pagano
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism*; D011379:Prognosis; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018570:Risk Assessment; D012720:Severity of Illness Index
D000959:Antihypertensive Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases