Objective:

Hemodymanic forces such as blood pressure and stretch induce myogenic contraction, the so-called "Bayliss effect". The molecules activated by stretch have some parallels with those in cerebral vasospasm (CVS) after subarachnoid hemorrhage (Nakayama et al. 2010). We aimed to clarify how the stretch-activated kinases and phosphatases, particularly those concerned with phosphorylation of 20kd myosin light chain (MLC), were involved in the development of CVS.

Methods and Results:

The progression of CVS was assessed in the two-hemorrhage canine model. Stretching of isolated canine basilar artery, at a rate of 1 mm/sec, from the initial length (Li) to 1.5 Li, increased MLC phosphorylation at Ser-19 and Thr-18 mediated by MLC-kinase and Rho-kinase, leading to contraction. Maintaining the stretched state, however, produced triphosphorylation of MLC20 at Thr-9, in addition to Ser-19 and Thr-18, and gradual relaxation. Two-dimensional phosphopeptide maps of MLC20 indicated that activation of protein kinase C (PKC) alpha-isoform mediated by protein phosphatase 2A (PP2A), was involved in the triphosphorylation of MLC20, which counteracted the myogenic contraction (Obara et al. 2010). However, mono- or diphosphorylated MLC level increased significantly in the CVS. Furthermore, PKC, in particular delta isoform, could mediate activation of caldesmon, an actin-linked contractile regulator, and enhanced CVS.

Conclusions:

The results suggest that in our modern sense of the "Bayliss effect" the autoregulatory myogenic response not only generates basal vascular tone, but also by inhibitory action prevents excessive vasoconstriction. In contrast, as to an underlying cause of CVS, the vasospastic contraction occurs in a positive feedback manner. An inhibitory action may fail in CVS.

Nakayama, K., et al. 2010. In: Mechanosensitivity in Cells and Tissues, eds. Kamkin, A. & Kiseleva, I. Springer, 3, 453–481.

Obara et al. 2010. J Vasc Res 47, 115–127.