Improvement of aortic wall distensibility and reduction of oxidative stress by pioglitazone in pre-diabetic stage of Otsuka Long-Evans Tokushima fatty rats.
We tested the hypothesis that pioglitazone (insulin sensitizer) reduces oxidative stress and improves aortic wall distensibility in the pre-diabetic stage of Otsuka Long-Evans Tokushima Fatty rats, type 2 diabetes mellitus (DM) model. 20 DM and 9 nonDM male rats were divided into 3 groups: treated-DM, untreated-DM, and untreated-nonDM. Pioglitazone (0.01%) was mixed in chow in the treated group from 15 to 20 weeks of age. At baseline and 20 weeks, plasma malondialdehyde (MDA) was measured. At 20 weeks, intravascular ultrasound images and aortic pressure were simultaneously recorded. Stiffness parameter beta was calculated from the cyclic variations of aortic diameter and pressure. From an excised thoracic aorta, aortic wall collagen was measured, and the morphology was histopathologically evaluated by hematoxylin-eosin staining. At 20 weeks, MDA (nmol/ml) in treated-DM (2.3 +/- 0.3) was lower than in untreated-DM (3.2 +/- 0.6, p < 0.0001). beta in treated-DM (0.53 +/- 0.21) was smaller than that in untreated-DM (0.88 +/- 0.26, p = 0.0067). Aortic wall collagen (mg/100 mg dry weight) did not decrease in treated-DM (22.3 +/- 3.2 vs untreated-DM : 19.6 +/- 4.7). Lumen/medial area ratio (L/M) increased in treated-DM (2.79 +/- 0.40 vs untreated-DM : 2.22 +/- 0.20, p = 0.0041, untreated-nonDM : 2.25 +/- 0.55, p = 0.0075). MDA was significantly correlated with beta (r = 0.65, p = 0.0005) or L/M (r = -0.60, p = 0.0008). Pioglitazone may reduce oxidative stress and contribute to improvement of aortic wall stiffness without decrease in collagen content at an early prediabetic stage of type 2 DM.
Tsuji
Teppei
T
Second Department of Internal Medicine, Kagawa Medical University, 1750-1, Miki, Kita, Kagawa 761-0793, Japan.
Mizushige
Katsufumi
K
Noma
Takahisa
T
Murakami
Kazushi
K
Miyatake
Akira
A
Kohno
Masakazu
M
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D000077205:Pioglitazone; D051381:Rats; D020334:Rats, Inbred OLETF; D013844:Thiazoles / Q000097:blood / Q000494:pharmacology*; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D013844:Thiazoles; D045162:Thiazolidinediones; D003094:Collagen; D000077205:Pioglitazone