HSP70 Contributes to Ca 2+ Handling in Phenylephrine‐induced Vascular Contraction

Heat‐shock protein 70 (HSP70), a housekeeper molecular chaperone, is an emerging player in vascular physiology. However, the specific mechanism(s) targeted by this protein in order to support this process is/are mostly unknown. The contraction of vascular structures primarily relies on changes in the intracellular concentration of Ca 2+ , and interestingly, previous studies have demonstrated that the genetic deletion of HSP70 affects Ca 2+ homeostasis, which worsens cardiac and skeletal muscle function. However, it is yet‐to‐be‐determined if HSP70 also contributes to Ca 2+ dynamics in vascular smooth muscle. To fill in this gap, in this study, we specifically investigated if pharmacological blockade of HSP70 impacts vascular contraction by impairing Ca 2+ handling mechanisms. To achieve such a goal, we performed functional studies in a wire myograph using aorta isolated from male Sprague Dawley rats. Experiments were conducted with and without exogenous Ca 2+ in the presence or absence of VER155008, a pharmacological inhibitor of HSP70. Functional studies were also conducted in the presence and absence of inhibitors for the major mechanisms contributing to phenylephrine‐induced contraction. Changes in the intracellular concentration of Ca 2+ were determined with a biochemical assay kit. Here, we report that blockade of HSP70 influences Ca 2+ handling mechanisms in phenylephrine‐stimulated aorta. More importantly, we provide evidence that this protein affects fast/phasic and prolonged/tonic contraction via crosstalk with inositol triphosphate receptor‐mediated Ca 2+ release and voltage‐independent Ca 2+ channels‐facilitated Ca 2+ influx, respectively. Together, our findings shed light on the mechanisms targeted by HSP70 in order to assist in vascular contraction and open research avenues for disease‐associated vascular complications.