HYPEROSMOLALITY-INDUCED ABNORMAL PATTERNS OF CALCIUM MOBILIZATION IN SMOOTH-MUSCLE CELLS FROM NONDIABETIC AND DIABETIC RATS

Hyperglycemia and/or hyperosmolality may disturb calcium homeostasis i n vascular smooth muscle cells (SMCs), leading to altered vascular con tractility in diabetes. To test this hypothesis, the KCl-induced incre ases in [Ca2+](i) in primarily cultured vascular SMCs exposed to diffe rent concentrations of glucose were examined. With glucose concentrati on in solutions kept at 5.5 mM, KCl induced a fast increase in [Ca2+]( i) which then slowly declined (type 1 response) in 83% of SMCs from no n-diabetic rats. In 9% of non-diabetic SMCs KCl induced a slow increas e in [Ca2+](i) (type 2 response). Interestingly, under the same cultur e conditions KCl induced type 1 and type 2 responses in 47 and 35% of SMCs from diabetic rats. When SMCs from non-diabetic or diabetic rats were cultured in 36 mM glucose, KCl induced a fast increase in [Ca2+]( i) which, however, maintained at a high level (type 3 response). The s ustained level of [Ca2+](i) in the presence of KCl was significantly h igher in cells cultured with 36 mM glucose than that in non-diabetic c ells cultured with 5.5 mM glucose. Furthermore, the hyperglycemia-indu ced alterations in calcium mobilization were similarly observed in cel ls cultured in high concentration of mannitol (30.5 mM) or L-glucose, indicating that hyperosmolality was mainly responsible for the abnorma l calcium mobilization in diabetic SMCs.