Determinations of Insulin Signaling Defects in the NTS Neurons of Spontaneously Hypertensive Rats

• Main Authors: Hsiao-Ning Huang, 黃曉寧
• Other Authors: none
• Format: Others
• Language: en_US
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/27404741149136919878

碩士 === 國立中山大學 === 生物醫學科學研究所 === 91 === Insulin resistance plays an intricate role in the development of cardiovascular diseases, hypertension is associated with insulin-resistant states such as diabetes and obesity. However, the underlying mechanism to explain the associations between hypertension and insulin resistance is unknown. The insulin exerts various biological effects in different type of cells. Clinical studies have reported that insulin has been shown to stimulate the protein kinase Akt via activation of PI3K in endothelial cells. Furthermore, insulin stimulated production of nitric oxide (NO) is inhibited by wortmannin in human umbilical vein endothelial cells (HUVECs). We also reported previously that NO contributes to the regulation of blood pressure in central nervous system. The aim of this study was to elucidate the potential mechanisms linking hypertension with insulin resistance and whether insulin signaling may involved in cardiovascular regulation in rat NTS neurons, we investigated the cardiovascular effects of insulin in the nucleus tractus solitarii (NTS) of urethane-anesthetized male spontaneous hypertensive rat (SHR) and normotensive Wistar-kyoto rats (WKY). Unilateral microinjection of insulin (100 IU/ml) into the NTS produced prominent depressor and bradycardic effects in 8/16 week-old WKY. However, no significant cardiovascular effects were found in adult SHR (16 week-old) after insulin injection. Furthermore, young SHR (8 week-old) with normal blood pressure showed depressor and bradycardic effects after insulin injection. Pretreatment with PI3K inhibitor LY294002 and NO synthase inhibitor L-NAME into the NTS attenuated the cardiovascular response evoked by insulin in WKY and young SHR but not in adult SHR. Furthermore, insulin induced Akt phosphorylation in-situ in WKY and SHR rats. Thus, these results indicated that insulin-PI3K-Akt-NOS sensitive mechanisms were involved in WKY and young SHR (normotensive) but not in adult SHR (hypertensive). The results also suggested the possible defective insulin signaling may resulted in the development of hypertension in adult SHR.