Mechanotransduction and the Myogenic Response in Diabetes - The Mechanobiology of Obesity and Related Diseases - page 227

Alterations in the regulation of myogenic vasoconstriction conceivably con-
tribute to a number of cardiovascular pathologies [ 8 ]. Depending on the type of
disorder, these phenomena include both increases and decreases in myogenic
responsiveness. To date, however, it is uncertain whether diabetes alters (increases
or decreases) myogenic vasoconstriction. Further, it is uncertain whether any
alteration is duration of diabetes-dependent such that increased myogenic reactivity
might be observed at, for example, an early phase of the metabolic disorder while
decreased reactivity is observed at a longer duration. Similarly, the degree of
metabolic derangement may differentially affect myogenic reactivity. Regardless of
these possibilities, vascular dysfunction and hence alterations in blood flow occur in
diabetes suggesting that local mechanisms regulating hemodynamics are either
inherently altered or overridden by factors associated with the metabolic disorder.
In this review, we first consider our current understanding of the cellular
mechanisms underlying the arteriolar myogenic response and subsequently how
alterations in these mechanisms are related to the progression of diabetes including
insulin resistance (a pre-diabetic state) and both type 1 and 2 diabetes. Owing to
the brief nature of this article a comprehensive list of prior studies is not provided
and readers are referred to more general reviews [ 2 , 3 , 9 - 13 ].
2 Myogenic Control of Blood Flow: Physiological
Relevance
Contraction of smooth muscle cells is crucial for blood vessels to alter their diameter
and thereby control blood flow. According to Pouiselle's Law, flow is related to the
fourth power of the vessel radius making arterial tone, the major determinant in the
regulation of local hemodynamics. Variation in artery diameter is accomplished by
active shortening of vascular smooth muscle cells (VSMCs), which are arranged
circumferentially or near perpendicular to the long axis of the vessel. A specific type
of smooth muscle constriction dominant in the microvasculature is myogenic, or
pressure-induced constriction of small arteries and arterioles, which underlies local
regulation of microvascular blood flow. Changes in intravascular pressure represent
an important mechanical stimulus that has a central role in 'autoregulation of blood
flow' whereby tissues are able to maintain perfusion requirements despite fluctua-
tions in arterial pressure [ 3 ]. In human subjects autoregulation typically occurs over a
systemic perfusion pressure range of 60-150 mmHg. Furthermore, myogenic con-
striction provides a level of basal tone upon which vasodilators, such as nitric oxide,
endothelium-derived hyperpolarizing factor(s), tissue metabolites (for example
adenosine) and pharmacological agents such as Ca 2+ channel blockers, can act to
lower resistance and match blood flow to changing metabolic demand. Conversely,
when perfusion pressure decreases, myogenic vasodilation acts to increase local
blood flow. An additional consequence of arteriolar myogenic responsiveness is its
contribution to regulating capillary hydrostatic pressure and, thus, modulation of
fluid flux across the vascular wall.