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Antioxidant and Angiotensin AT1 Receptor Antagonist Treatment Reduced the Hypertension Induced by Chronic Intermittent Hypoxia in rats, but had Different Effects on Endothelial Dysfunction
Author(s) -
Iturriaga Rodrigo,
Krause Bernardo,
Casanello Paola,
Dias Ana CR,
Arias Paulina,
Del Rio Rodrigo
Publication year - 2016
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.30.1_supplement.986.4
Subject(s) - losartan , medicine , endothelial dysfunction , endocrinology , blood pressure , angiotensin ii , electrical impedance myography , angiotensin ii receptor type 1 , vasodilation
Chronicintermittent hypoxia (CIH) produces sympathetic hyperactivity and oxidative stress, leading to endothelial dysfunction and systemic hypertension. Concomitant administration of the antioxidant N‐acetylcysteine (NAC) and the AT1 receptor blocker Losartan ® , before and during CIH prevented the hypertension in rats. However, it is not known if treatments with NAC and/or Losartan ® are able to reduce arterial blood pressure and improve the endothelial function when rats became hypertensive due to CIH exposure. Thus, we studied if NAC and Losartan ® may revert the hypertension and endothelial dysfunction in CIH‐hypertensive rats. Male Sprague‐Dawley rats (200 g) were exposed to CIH (5%O 2, 12 times/h 8 h/day) or sham condition for 28 days. After 14 days, CIH‐rats were treated with NAC (400 mg/kg/day in drinking water) or Losartan ® (3mg/kg/day with osmotic pump) until the day 28. Arterial blood pressure (BP) was continuously measured with radio‐telemetry in conscious rats, and at day 28 the external carotid arteries (2mm) were isolated to measure vasoactive responses to KCl (10–125 mM) and acetylcholine (ACh, 10 −10 –10 −5 M) using wire‐myography. CIH increased mean BP (≈ 10 mmHg) after 3 days of exposure. NAC reduced the elevated BP towards normal values (100.0±2.2 mmHg) in 6–8days despite of CIH exposure, while Losartan ® reduced the elevated BP in 2 days below the normal values(89.0±2.0 mmHg). External carotid arteries from CIH‐rats showed higher active contraction induced by KCl (3.8±0.4 vs. 2.3±0.3 N/m 2 ) and reduced relaxation to ACh (11.4±1.2 vs. 24.8±3.9 %max) related to sham rats. NAC did not reverse the increased contraction induced by KCl (3.9±0.3 N/m 2 ), and failed to restore the impaired ACh‐induced relaxation in carotid arteries (9.9±1.1%max). Losartan ® also failed to reverse the increased vessel contraction induced by KCl (3.7±0.4 N/m 2 ), but improved the ACh‐induced relaxation (40.6±5.1 %max). Present results suggest that NAC and Losartan ® reverts the CIH‐induced hypertension, but have different effects on the altered endothelial and contractile artery properties in rats exposed to CIH. Support or Funding Information Supported by FONDEF D11I1098.