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transmitted downstream in the vessels exposed to the ramp increase. Analogous to
these arterioles from STZ-induced diabetic rats are stiffer and show a decrease in
the transient Ca 2+ rise in response to a stepwise increase in intraluminal pressure
[ 111 , 160 ]. Similarly, in vivo experiments, arterioles of STZ-treated animals
showed no response to transient increases in pressure [ 112 ]. These studies sug-
gested that vessels in the diabetic animals were behaving more like a rigid tube
than a distensible blood vessel and as a result the effectiveness of myogenic
regulation was impaired. Complicating this interpretation was that the diabetic
animals showed smaller arteriole diameters and increased steady-state tone.
5.4 Alterations in Contractile Mechanisms Impacting
Arteriolar Myogenic Signaling
As myogenic signaling utilizes a number of molecules involved in other modes of
contraction (including agonists and direct depolarization), diabetes-induced
alterations in any of these will also likely manifest in alterations in mechano-
transduction. For example a considerable body of evidence has accumulated in
diabetes-induced changes in smooth muscle cell Ca 2+ handling and ion channel
activity (including VGCCs, TRPs, BK Ca , Kv and K ATP )[ 113 , 115 , 168 - 172 ].
Similarly, dysfunction at the level of the contractile proteins, mechanisms
underlying modulation of Ca 2+ sensitivity and cytoskeletal involvement would be
expected to impact various modes of contractile activation.
6 Concluding Remarks and Future Directions
There is no doubt that diabetes impacts the vasculature at multiple levels resulting
in changes to both the physical and functional properties of small arteries (Fig. 3 ).
In regard to mechanotransduction pathways, and in particular myogenic respon-
siveness, it remains unclear whether any diabetes-induced alteration is specific to
the signaling mechanisms underlying myogenic responsiveness, contractile acti-
vation, per se, or occurs secondary to co-existing vascular dysfunction. An
example of the latter perhaps includes inflammatory reactions leading to altera-
tions in the production of paracrine-acting factors that alter vascular responsive-
ness. The disturbed vascular function then manifesting as an alteration in
mechanically induced signaling. Similarly, vascular remodeling processes (at the
vessel wall, ECM and cellular levels) may impact the ability of vessels to sense
and respond to mechanical stimuli. Understanding such relationships is also made
difficult by gaps in our knowledge regarding the exact signaling mechanisms that
mediate the transduction of a mechanical stimulus into an appropriate vasomotor
event. Given the strong possibility that myogenic signaling involves interactions
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