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Objective: Insulin and insulin-like growth factor-1 (IGF-1) have vasorelaxant effects in vivo, which is dependent on nitric oxide (NO) production. The aim of this study was to investigate the vasorelaxant responses mediated by insulin and/or IGF-1 in aortas of obese Zucker rats. Methods: The thoracic aortas of eight lean and eight obese Zucker rats (6 months old) were isolated for vasorelaxation analysis. Insulin-induced and IGF-1-induced vasorelaxant responses were evaluated by the isometric tension of aortic rings in the organ bathes. The roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS) in vasorelaxant responses were examined by treating selective inhibitors, such as wortmannin (an inhibitor of PI3K) and N o -nitro-L-arginine methyl ester (L-NAME, a NOS inhibitor). In addition, the vascular responses to sodium nitroprusside (SNP), a direct vasodilator of vascular smooth muscle, were examined. Results: The insulin-induced vasorelaxation in aortas of obese rats was significantly decreased, whereas the IGF-1-induced vasorelaxation was significantly increased, compared with that in lean rats. After the pre-administration of wortmannin or L-NAME, the altered insulin-induced or IGF-1-induced vasorelaxation was abolished. There was no significant difference in the SNP-induced vasorelaxation between lean and obese rats. Conclusion: Our findings suggested that the decreased insulin-mediated vasorelaxation in obese rats appeared to be counteracted by the increased IGF-1-mediated vasorelaxation. Furthermore, the NO-dependent pathway was involved in the altered vasorelaxant responses. However, the SNP-induced vasorelaxation was not changed in obese rats.

Postmenopause, characterized by estrogen deficiency, contributes to the risk of cardiovascular dysfunction. The purpose of this study was to investigate the combined effects of chronic exercise and estrogen on vascular function in ovariectomized rats. Fifteen‐week‐old female Sprague‐Dawley rats were randomly assigned into 3 groups: sham‐operated (sham), ovariectomized (OVX), and OVX with given exercise and 17 beta‐estradiol injection (OVX+Ex+E2) groups. The thoracic aortas were dissected for acetylcholine (ACh)‐ and insulin‐like growth factor‐1 (IGF‐1)‐mediated vasodilation analysis. To explore the roles of phosphatidylinositol‐3 kinase (PI3K) and NO synthase (NOS), selective inhibitors (i.e., wortmannin and Nω‐nitro‐L‐arginine methyl ester) were used. Sodium nitroprusside (SNP, a NO donor)‐induced vasodilation was also examined. We found that, 1) compared with sham rats, the vasodilation evoked by ACh and IGF‐1 was significantly deteriorated in OVX rats, but the effects were disappeared after the removal of endothelium; 2) the combined intervention significantly improved ACh‐ and IGF‐1‐mediated vasodilation in OVX rats; 3) these altered vascular responses were mainly mediated by the release of PI3K and NOS; 4) no significant difference in SNP‐mediated vasodilation was found among three groups. According to our results, we suggested that chronic exercise and estrogen may cooperatively reverse postmenopause‐altered vascular function.

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