Angiotensin-II receptor blocker exerts cardioprotection in diabetic rats exposed to hypoxia.
BACKGROUND
Hypoxia caused by sleep apnea might be associated with an increased risk of cardiovascular events in subjects with metabolic syndrome. The aim of this study was to examine the effect of hypoxia on the left ventricular (LV) myocardium and evaluate the cardioprotective effect of an angiotensin-II receptor blocker (ARB) in diabetic rats.


RESULTS
Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats at 30 weeks of age (n=30) were divided into 2 groups that were treated with vehicle or candesartan 0.2 mg x kg(-1) x day (-1). The animals were housed in a hypoxic gas chamber (oxygen, 10.0+/-0.5%, mean +/- standard deviation) for 2 weeks. Hypoxia increased right ventricular (RV) systolic pressure (hypoxia; 78+/-14 mmHg vs control; 22+/-5, p<0.05), but did not increase LV systolic pressure (131+/-23 mmHg vs 121+/-10). Hypoxia exacerbated the degeneration of cardiomyocytes, and accelerated the expression of hypoxia inducible factor-1alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF) in the myocardium. Treatment with ARB decreased RV and LV pressures (46+/-7 and 100+/-18 mmHg, respectively), suppressed the expression of HIF-1alpha and VEGF, and preserved the fine structure of the LV myocardium.


CONCLUSIONS
ARB exhibited cardioprotection under hypoxia, in part through the reduction of blood pressure and cytokine expression, in OLETF rats. Thus, ARB might be a potent agent for the treatment of diabetic patients with the complication of sleep apnea.
Inamoto
Sakiko
S
Third Department of Medicine, Osaka Medical College, Takatsuki, Japan.
Hayashi
Tetsuya
T
Tazawa
Naoko
N
Mori
Tatsuhiko
T
Yamashita
Chika
C
Nakano
Daisuke
D
Matsumura
Yasuo
Y
Okuda
Nobuaki
N
Sohmiya
Koichi
K
Sakai
Akiko
A
Furuya
Eisuke
E
Kitaura
Yasushi
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental; D004353:Drug Evaluation, Preclinical; D005786:Gene Expression Regulation / Q000187:drug effects; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D012891:Sleep Apnea Syndromes / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D013777:Tetrazoles / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D016276:Ventricular Function / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C081643:candesartan