Abnormalities of sarcoplasmic reticulum Ca2 mobilization in aortic smooth muscle cells from streptozotocin-induced diabetic rats

作者：Ma, Li; Zhu, Banghao^*; Chen, Xiangping; Liu, Jie; Guan, Yongyuan; Ren, Jun

来源：CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, 2008, 35(5-6): 568-573.

DOI：10.1111/j.1440-1681.2007.04832.x

• aortic smooth muscle cell
• diabetes
• inositol 1
• 4
• 5-trisphosphate-sensitive Ca(2 )store
• ryanodine-sensitive Ca2 store

1. Previously, we found that contractions in response to receptor-dependent (i.e. alpha(1)-adrenoceptor agonist phenylephrine) and -independent (i.e. cyclopiazonic acid) stimuli are decreased in rat aorta during late diabetes. The aim of the present study was to further investigate the changes of intracellular Ca2+ homeostasis in diabetic aortic smooth muscle cells. Functional changes of inositol 1,4,5-trisphosphate (IP3)- and ryanodine-sensitive Ca2+ stores of the sarcoplasmic reticulum (SR) were evaluated using Fluo-3 acetoxymethyl ester fluorescence, western blot and organ bath techniques.
2. In aortic smooth muscle cells from diabetic rats, the Ca2+ release and Ca2+ influx caused by both 10 mmol/L phenylephrine (depletion of IP3-sensitive Ca2+ stores) and 1 mmol/L ryanodine (depletion of ryanodine-sensitive Ca2+ stores) were both significantly decreased compared with control. Moreover, protein expression levels of IP3 (260 kDa) and ryanodine receptors (500 kDa) were reduced by 31.8 +/- 7.7 and 69.2 +/- 8.4%, respectively, in aortas from diabetic rats compared with those from control rats.
3. In diabetic rat aorta, phenylephrine-induced contractility was decreased to approximately two-thirds of that in controls, whereas ryanodine alone did not cause obvious contraction in aortas from either control or diabetic rats.
4. The present results suggest that the hyporeactivity of aortic smooth muscle to vasoconstrictors in diabetes results mainly from changes to the IP3-sensitive Ca2+ release pathway. The SR Ca2+ signalling pathway plays a crucial role in the development of diabetic vascular complications.

• 出版日期2008-6
• 单位中山大学