Differential Changes of Aorta and Carotid Vasodilation in Type 2 Diabetic GK and OLETF Rats: Paradoxical Roles of Hyperglycemia and Insulin

  • Mei-Fang Zhong
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
  • Wei-Li Shen
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
  • Masaki Tabuchi
    Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
  • Kyoko Nakamura
    Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
  • Yi-Chen Chen
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
  • Cong-Zhen Qiao
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
  • Jin He
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
  • Jie Yang
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China
  • Chuan Zhang
    Division of New Drug Research, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
  • Zdravko Kamenov
    Clinic of Endocrinology, Medical University-Sofia, 1431 Sofia, Bulgaria
  • Hideaki Higashino
    Department of Pharmacology, Kinki University School of Medicine, Osaka 589-8511, Japan
  • Hong Chen
    Department of Pharmacology and Shanghai Key Laboratory of Vascular Biology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 280 South Chong Qing Road, Shanghai 200025, China

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<jats:p>We investigated large vessel function in lean Goto-Kakizaki diabetic rats (GK) and Otsuka Long-Evans Tokushima Fatty diabetic rats (OLETF) with possible roles of hyperglycemia/hyperosmolarity and insulin. Both young and old GK showed marked hyperglycemia with normal insulin level and well-preserved endothelium-dependent and endothelium-independent vasodilation in aorta and carotid artery. There were significant elevations in endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive heme oxygenase (HO-1/HO-2) in GK. The endothelium-dependent vasodilation in GK was inhibited partly by NOS blockade and completely by simultaneous blocking of HO and NOS. In contrast, OLETF showed hyperinsulinemia and mild hyperglycemia but significant endothelium dysfunction beginning at early ages with concomitantly reduced eNOS. Insulin injection corrected hyperglycemia in GK but induced endothelium dysfunction and intima hyperplasia. Hyperglycemia/hyperosmolarity<jats:italic>in vitro</jats:italic>enhanced vessel eNOS/HO. We suggest that hyperinsulinemia plays a role in endothelium dysfunction in obese diabetic OLETF, while hyperglycemia/hyperosmolarity-induced eNOS/HO upregulation participates in the adaptation of endothelium function in lean diabetic GK.</jats:p>

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