Age‐dependent stretch‐induced myofilament calcium sensitization in ovine cerebral arteries

Abstract

Myogenic tone is a well‐established characteristic of cerebral arteries, but the mechanisms of this response are not fully understood, particularly in immature cerebral arteries. Given that myofilament calcium sensitivity is typically greater in fetal than adult cerebral arteries, we explored the hypothesis that the characteristics of myogenic tone should differ in fetal and adult arteries. To test this idea, we measured intracellular calcium via Fura‐2 in intact ovine posterior communicating arteries and found that stretch induced a graded increase in calcium (max ?ratio = .292), but only in adult arteries even though the magnitudes of stretch‐induced contraction were similar in adult (265% Kmax) and fetal (247% Kmax) arteries. Maximum levels of stretch‐induced myosin light chain (MLC) phosphorylation were also similar (?41–44%) in fetal and adult arteries. However, when length‐tension measurements were performed in permeabilized arteries held at pCa 7, graded stretch produced graded increases in force that were greater in adult (207% Kmax) than fetal (110% Kmax) arteries, indicating stretch‐induced calcium sensitization. Similar results were obtained at pCa 5.5. Together, these results indicate that myogenic tone is of greater magnitude in adult than fetal posterior communicating arteries, and that this difference is due to a greater calcium transient and a greater calcium sensitization response in adult compared to fetal arteries.Supported by NIH HD31226 and HL54120.