Enhanced platelet release of superoxide anion in systemic hypertension: role of AT1 receptors.
BACKGROUND
Enhanced oxidative stress has been observed in hypertension, but the underlying mechanism has not been fully clarified.


OBJECTIVE
To study the relationship between oxygen free radicals and hypertension, using platelets as a tool to measure the cellular production of superoxide anion (O2).


METHODS
Forty patients with hypertension were allocated randomly to groups to receive either irbesartan, an inhibitor of angiotensin II type 1 (AT1) receptors (n = 20), or a diuretic (hydrochlorothiazide) (n = 20). In each patient, collagen-induced production of O2 by platelets was studied before and after 4 weeks of treatment. Forty sex- and age-matched healthy individuals were studied as controls.


METHODS
Platelet-produced O2 was measured using lucigenin chemiluminescence and hydroethidine cytofluorimetric analysis.


RESULTS
Compared with healthy individuals, patients with hypertension showed a greater production of O2 by platelets (P < 0.001); there was no correlation between blood pressure and platelet O2 production. After treatment, no changes in platelet O2 formation were observed in patients receiving hydrochlorothiazide; conversely, those treated with irbesartan showed a significant (P < 0.001) decrease in platelet O2 production. At the end of the treatment, no differences in blood pressures were observed between the two groups. In-vitro incubation of platelets with angiotensin II elicited a significant increase in O2 (P < 0.001) that was dose-dependently inhibited by irbesartan and diphenylene iodonium, an inhibitor of NADPH oxidase.


CONCLUSIONS
Patients with hypertension showed an enhanced formation of O2 in platelets that was not dependent on blood pressure but could be mediated by AT1 receptors via NADPH oxidase activation.
Germanò
Giuseppe
G
Department of Experimental Medicine and Pathology, University of Rome 'La Sapienza', Rome, Italy.
Sanguigni
Valerio
V
Pignatelli
Pasquale
P
Caccese
Daniela
D
Lenti
Luisa
L
Ragazzo
Maddalena
M
Lauro
Renato
R
Violi
Francesco
F
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D004232:Diuretics; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use; D013481:Superoxides / Q000097:blood*; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004232:Diuretics; D044140:Receptor, Angiotensin, Type 1; D049993:Sodium Chloride Symporter Inhibitors; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D013481:Superoxides; D019255:NADPH Oxidases; D000077405:Irbesartan