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Antihypertensive efficacy of adaptation to intermittent hypoxia vs nitric oxide donor and beta‐blocker therapies
Author(s) -
Manukhina Eugenia B.,
Pokidyshev Dmitry A.,
Smirin Boris V.,
Mashina Svetlana Yu.,
Buvaltsev Valery I.,
Downey H. Fred,
Malyshev Igor Yu.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a822-a
Subject(s) - vasoprotective , enos , nebivolol , nitric oxide , medicine , hypoxia (environmental) , endocrinology , endothelial dysfunction , pharmacology , chemistry , nitric oxide synthase , blood pressure , oxygen , organic chemistry
Adaptation to intermittent hypoxia (AIH) may provide an antihypertensive therapy due to its ability to activate endothelial NO synthase (eNOS). We compared the antihypertensive effects of AIH, a NO donor, and a β‐blocker which also stimulates eNOS. Spontaneously hypertensive rats (SHRSP) were treated with AIH, 40 daily 5‐h sessions at simulated altitude of 5,000 m; NO donor dinitrosyl iron complex (DINC, 170 μg/kg i.p., every 4th day for 40 days); β‐blocker nebivolol (1.25 mg/kg i.p. daily for 40 days). AIH and DNIC decreased BP in SHRSP to a similar extent (from 219±19 to 156±17 mm Hg, P <0.001 and to 165±18 mm Hg, P <0.01, respectively). AIH exerted a vasoprotective effect as evidenced by improved endothelium‐dependent relaxation to acetylcholine of isolated rat aorta (33±4.0% vs. 18±2.2% in untreated rats, P <0.01), whereas DNIC did not improve endothelial function. Nebivolol exerted both antihypertensive (176±12 mm Hg, P <0.05) and vasoprotective effects (27±2.9%, P <0.05), but these effects were less pronounced than those of AIH. Thus, as an antihypertensive therapy, AIH was superior to either a NO donor or a β‐blocker that stimulates eNOS. The superiority of AIH may be due to its ability to induce expression of eNOS gene as well as stimulate eNOS activity, generate NO stores in the vascular wall, activate protective antioxidant enzymes. In conclusion, AIH is a promising antihypertensive therapy.