Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 431

Mechanotransduction may also be mediated by cAMP messenger. Repeated
cyclic strain on cultured smooth myocytes of coronary arteries reduces adenylate
cyclase activity and cAMP [ 803 ]. Decrease in activity of adenylate cyclase, hence
cAMP level, can result from applied cyclic stretching on SMC in vivo [ 804 ].
Owing to Ca 2 + influx, myosin light chain kinase activates myosin light chains
to initiate contraction. Blood vessels rely on auto- and paracrine mechanisms to
immediately react to hemodynamical changes.

8.5.8.3 Endothelium-Dependent Regulation of the Vasomotor Tone

Endothelial regulators of the vasomotor tone are vasoactive substances released
from the endothelium in response not only to humoral, but also mechanical
stresses, to act on smooth myocytes (Chap. 9 ). In addition, mechanical stresses can
provoke charge changes in the subendothelial layer that can modify cell membrane
polarization. Cultured endothelial cells are sensitive to environmental charges as
well as frequency and modulation rate of charge changes.
Blood friction along the wall luminal surface is sensed by endothelial cells
and transduced into chemical reactions. Wall shear stress can excite plasmalemmal
G-protein-coupled receptors via membrane tension [ 805 ]. Adaptation to flow forces,
in paricular, results from cytoskeleton reorganization that enables a redistribution
of intracellular forces [ 806 ]. Actin-based stress fibers align with flow direction.
Mechanical forces are transmitted by the plasma membrane and cytoskeleton to the
entire cell, and then to adjacent cells, basement membrane, and the entire extracel-
lular matrix. Actin filaments anchored to the nucleus membrane via transmembrane
proteins as well as intercellular and cell-matrix adhesion proteins, 74

are the main

transmission elements.
Interactions between integrins and matrix constituents determine tensional
integrity (tensegrity) of the cells. Tensegrity models have been proposed for active
cytoskeleton reaction [ 808 ]. Actin filaments are also required in signal transduction
that involves adenylate cyclases and stretch-activated ion channels.
Hemodynamic forces imposed on endothelial wetted surface trigger the synthesis
of either vasodilators, such as nitric oxide and prostacyclin, or vasocontrictors,
such as endothelin-1 75

(local flow-induced regulation of the blood
circulation). Stress increase causes SMC relaxation.
Molecules released by endothelial cells act locally on underlying smooth my-
ocytes to modulate the vasomotor tone [ 809 ]. Several biochemical systems are
involved: (1) activation of plasmalemmal ion channels 76 and receptors; (2) reaction

and PGf2 α

74 Actin filaments bind to integrins by

-actinin, talin, and vinculin [ 807 ].
75 Endothelin, a strong vasoconstrictor, also causes myocardium contraction, ANP secretion, and
SMC division.
76 For example, the release of vasodilators is associated with activation of plasmalemmal K +
channels of endothelial cells.

α