Effect of long-term irbesartan treatment on endothelium-dependent vasodilation in essential hypertensive patients.
Endothelial dysfunction plays a pivotal role in the development of essential hypertension and its complications. The purpose of this study is to assess the effect of antihypertensive treatment with the angiotensin receptor blocker irbesartan on endothelial function in a group of essential hypertensive patients. Thirty-two untreated hypertensives are examined at baseline and at the end of a six-month period of irbesartan treatment. Endothelium-dependent and -independent responses are determined by measuring changes in forearm blood flow (FBF) by strain gauge plethysmography in response to intrarterial infusions of acetylcholine (endothelium-dependent vasodilation [EDV]), sodium nitroprusside (endothelium-independent vasodilation [EIV]), with and without the addition of the nitric oxide (NO) synthase inhibitor L-NMMA. Plasma endothelin, plasma and urinary nitrates and nitrites, and cyclic GMP are measured at baseline and at the end of treatment. Irbesartan promoted a significant increase in EDV (from 433+/-147% to 488+/-75%; P=0.027) and EIV (from 442+/-130% to 495+/-104%; P=0.041). L-NMMA-induced vasoconstriction was significantly enhanced after irbesartan treatment (relative decrease of FBF from 33.4+/-9.5% to 39.5+/-5.6%; P=0.001). Plasma concentrations of endothelin fell significantly after irbesartan treatment (from 5.78+/-1.86 to 4.16+/-1.52 pg/mL; P=0.001). We concluded that long-term irbesartan treatment enhances both endothelium-dependent and -independent vascular vasodilation capacity. In addition to this non-specific effect, irbesartan restores the vasoconstriction capacity of NO synthase inhibitors, suggesting a direct effect on tonic NO release, and decreases endothelin production. These actions may play an important role in the vascular protecting effects of irbesartan.
Bragulat
E
E
Hypertension Unit, Department of Internal Medicine, IDIBAPS, Hospital Clínic, University of Barcelona, Spain.
Larrousse
M
M
Coca
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A
de la Sierra
A
A
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000077405:Irbesartan