Effect of doxazosin on oxidative stress related proteins in essential hypertensive patients.
The role of oxidative stress in the pathophysiology of hypertension has stimulated the investigation of strategies to reduce oxidative stress via antioxidant defenses. Using a molecular biology approach, we report, in essential hypertensive patients, the effect of doxazosin treatment on the mononuclear cell gene and protein expression of two major elements in the oxidative stress and vascular remodeling-related pathways: p22(phox) and PAI-1. Ten essential hypertensive patients were treated with Doxazosin (4 mg/day) for two weeks (EH + D) and compared with ten untreated hypertensive patients (EH) and ten normotensive subjects (C). In EH p22(phox) and PAI-1 mRNA and protein level was increased compared with C. In EH + D, doxazosin reduced p22(phox) and PAI-1 gene and protein expression, which was similar to that of C. These results demonstrate for doxazosin an inhibitory effect on oxidative stress related proteins at gene and protein level, which confirms at molecular level a powerful antioxidant potential for this agent that could translate, in the long term, into a powerful antiatherosclerotic effect.
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova, Italy. renzcalo@unipd.it
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Calò
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Bertipaglia
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Pagnin
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Davis
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Sartori
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Semplicini
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Pessina
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D017292:Doxazosin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D019255:NADPH Oxidases; C086986:CYBA protein, human; D017292:Doxazosin