Mechanotransduction and the Myogenic Response in Diabetes - The Mechanobiology of Obesity and Related Diseases - page 228

As mentioned above, myogenic reactivity of the intact vascular network
interacts with other regulatory mechanisms including neurohumoral regulation.
Adrenergic stimulation enhances myogenic vasoconstriction in some vascular beds
through interaction of underlying cellular signaling mechanisms [ 4 ]. Moreover,
autoregulatory events persist during agonist-induced contractile activation such
that myogenic mechanisms may be activated by the hemodynamic changes that
follow the actual response to the agonist. Thus, the overall local vascular response,
and specifically the net effect on vascular resistance, can be a composite effect of
both neurohumoral and myogenic components [ 5 ]. Importantly, interactions also
occur between local regulatory mechanisms. For example, shear (flow)-dependent
mechanisms affect the level of basal tone upon which myogenic constriction
occurs [ 14 ].
The contribution of myogenic responsiveness to the regulation of local micro-
vascular hemodynamics raises a number of questions when considering patho-
physiological conditions involving vascular dysfunction (for example, hypertension,
vasospasm, vascular complications associated with insulin resistance and overt
diabetes). If microvascular hemodynamics are altered under disease-related situa-
tions, do these reflect specific defects in myogenic regulation or are local regulatory
mechanisms over-ridden by local factors or alterations in vascular structure
(remodeling)? Regardless of which, alterations in local blood flow control, and
specifically myogenic reactivity, conceivably contribute to vascular dysfunction.
3 Current Understanding of the Cellular Mechanisms
Underlying Myogenic Vasoconstriction
A schematic diagram illustrating events and mechanisms underlying the myogenic
response is shown in Fig. 1 . While this outline is presented as a single linear
pathway it is highly likely that parallel pathways exist. For example, multiple
detection mechanisms may exist and/or an alteration in intraluminal pressure may
simultaneously activate events modulating the contractile proteins and organization
of the cytoskeleton/extracellular adhesions.
3.1 Sensed Variables
A limiting factor in our understanding of myogenic constriction has been a lack of
knowledge of what the sensed variables are and how they are transduced to an
appropriate cellular reaction. Abundant evidence indicates that myogenic con-
traction is an inherent property of VSMCs and does not directly require other cell
types including the endothelium [ 15 - 17 ]. An increase in intraluminal pressure
presumably imparts its effect through a mechanical property such as smooth