Arteriolar Myogenic Response During Clamping of Intracellular Vascular Smooth Muscle Calcium Using BAPTA

Arteriolar myogenic responses to increased intravascular pressure are accompanied by elevated [Ca 2+ ] i in vascular smooth muscle (VSMC). In this study, we investigated the Ca 2+ dependence of the mechanotransduction process in single cells and in intact arterioles. Using atomic force microscopy (AFM), with AFM probes coated with fibronectin, we applied stretching forces to single VSMC focal adhesion sites. We found that the VSMCs responded with a contractile response that did not depend on an increase in [Ca 2+ ]i. Furthermore, loading VSMCs with BAPTA*AM, an intracellular Ca 2+ chelator, paradoxically resulted in further enhancement of the stretch induced VSMC contractile response. These data suggest a role for a Ca 2+ independent mechanism. To further examine whether this same mechanism operated in intact arterioles, the effect of BAPTA was examined in isolated rat cremaster muscle feed arterioles (~150 μm Dia.). The arteriolar myogenic response was compared at pressure steps from 60–140 mmHg before and after loading of BAPTA. BAPTA loading enhanced arteriolar myogenic tone compared to control vessels. In endothelium‐denuded vessels, a BAPTA enhancement was also observed suggesting it was affecting the VSMC directly. These data support the presence of an important Ca 2+ independent mechanism in mediating mechanotransduction in VSMC. ( P01HL095486 to G.A.M. and AHA 0835676N to Z.S.)