Salidroside improved cerebrovascular vasodilation in streptozotocin-induced diabetic rats through restoring the function of BKCa channel in smooth muscle cells.

Abstract

Vessel disease is a kind of severe complication in diabetic patients. However, few pharmacologic agents can directly recover diabetic vascular function. Salidroside (SAL), a major ingredient from Rhodiola rosea, has been found to have an obvious hypoglycemic effect and a beneficial protection on vascular function in diabetes. However, whether SAL is a suitable treatment for diabetes has not so far been evaluated and the underlying mechanisms remain unknown. The present work aims to (1) investigate the potential effects of SAL on cerebrovascular relaxation in streptozotocin-induced diabetic rats or when exposed to acute hyperglycemia condition and (2) examine whether function of the BKCa channel is involved in SAL treatment for diabetic vascular relaxation. Our results indicate that chronic administration of 100mg/kg/day SAL not only improves cerebrovascular relaxation but also increases BKCa β1-subunit expressions at both protein and mRNA levels and enhances BKCa whole-cell and single-channel activities in cerebral VSMCs of diabetic rats. Correspondingly, acute application of 100 μM SAL induces cerebrovascular relaxation by activation of the BKCa channel. Furthermore, SAL activated the BKCa channel mainly through acting on the β1-subunit in HEK293 cells transfected with hSloα+β1 constructs. We concluded that SAL improved vasodilation in diabetic rats through restoring the function of the BKCa-β1 subunit in cerebrovascular smooth muscle cells, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes.