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Impaired Vasorelaxation of Coronary Arteries in Cynomolgus Monkeys with Diabetes
Author(s) -
Katakam Prasad VG,
Kavanagh Kylie,
Jarajapu Yagna PR,
Snipes James A,
Tulbert Christina D,
Rowe Patrick,
Wagner Janice D,
Busija David W
Publication year - 2006
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.20.4.a728-c
Subject(s) - enos , medicine , coronary arteries , diabetes mellitus , endocrinology , endothelial dysfunction , nitric oxide , vasodilation , sodium nitroprusside , type 2 diabetes , insulin , vascular smooth muscle , endothelium , cardiology , nitric oxide synthase , artery , smooth muscle
Diabetes promotes enhanced cardiovascular morbidity and mortality. We investigated the coronary vascular function in cynomolgus monkeys which were shown to develop accelerated atherosclerosis with diabetes. Methods Monkeys on an atherogenic diet were randomized to control and diabetic groups. Diabetes was induced by streptozotocin injection and blood glucose was controlled with insulin. Following one month of diabetes, vasorelaxation to acetylcholine (ACh) or nitroprusside (SNP) was evaluated in vitro in coronary arteries (<300 μm). Superoxide (SO) production in carotid arteries was measured by chemiluminescence. Endothelial nitric oxide synthase (eNOS) and Cu/Zn superoxide dismutase (SOD) expression in homogenates of hearts was assessed with real time PCR and immunoblotting. Results Diabetic monkeys had elevated blood glucose and impaired glucose tolerance as compared to control. Vasorelaxation to ACh as well as the SNP was diminished in diabetic coronary arteries. SO production was elevated in diabetic arteries. Expression of eNOS was enhanced in diabetic arteries while Cu/Zn SOD expression was similar compared to control arteries. Conclusions Coronary arteries of diabetic monkeys manifest impaired endothelium and smooth muscle dependent vasorelaxation despite enhanced expression of eNOS. Elevated SO may mediate vascular dysfunction by decreasing NO bioavailability and by altering smooth muscle relaxation (Support: NIH grants HL‐30260, HL‐46558, HL‐50587, DK‐62372).