Mechanotransduction and the Myogenic Response in Diabetes - The Mechanobiology of Obesity and Related Diseases - page 246

mesenteric arteries, coronary arteries from 22-week-old GK rats developed less
tone than arteries from control rats [ 128 ].
Another type 2 diabetic rat model is obese BBZDR/Wor rat, which represents
hyperlipidemia, hyperleptinemia, insulin resistance and hyperglycemia [ 131 ]. This
animal model has also showed inconsistent myogenic responses based on vascular
beds. For example, in the posterior cerebral artery, similar myogenic responses
were observed at 4 weeks of diabetes and their age-matched control rats at pres-
sure between 70 and 200 mmHg, while arteries from 5 or 8 months diabetic rats
showed higher myogenic tone at pressures higher than 30 mmHg, suggesting that
longer duration of diabetes increased myogenic tone in the cerebral arteries from
the BBZDR/Wor diabetes model [ 132 ]. From the same group and same animal
model, Ito et al. indicated that at the prediabetic age of 10 weeks, pressure-
myogenic tone curves were comparable, while 3 months of diabetes decreased
myogenic tone in the ophthalmic arteries [ 133 ].

4.2 Human Studies

Relative to the animal studies comparatively few direct studies of arteriolar
myogenic responsiveness have been performed in human tissues. This is due, in
large part, to difficulties in acquiring reproducible human tissues. Surprisingly,
myogenic responsiveness in human arteries is either consistently decreased or
unchanged regardless of factors such as vascular bed, type of diabetes and methods
used (Table 1 ). For example, Feng et al. showed that ET-1 induced contraction
was decreased in the left internal mammary artery from diabetic patients compared
to non-diabetic individuals [ 134 ]. In the subcutaneous gluteal fat artery, Schofield
et al. reported that vessels from type 2 diabetic patients showed decreased myo-
genic responsiveness compared with control patients [ 135 ]. In addition, Lorenzi
et al. reported absent myogenic responses in diabetic subjects [ 136 ]. However, in
coronary arterioles, myogenic tone was unaffected by both type 1 and 2 diabetes
[ 137 , 138 ]. However, it should be noted that human studies typically have several
limitations as individuals often have coexisting morbidities including hyperten-
sion, hypercholesterolemia, atrial fibrillation and obesity that may impact on
alteration in myogenic reactivity.
An alternate approach to direct assessment of myogenic reactivity that can be
used in human subjects involves examining vascular responses to changes in
posture. For example Lorenzi et al. measured steady- state retinal artery diameter
(superior temporal artery, diameter approximately 120 mm) while sitting and
following reclining. A normal response on reclining was expected to be a decrease
in diameter of the retinal artery resulting from active myogenic constriction as a
consequence of the postural increase in perfusion pressure. In this study the
Authors demonstrated that a subset of type 1 diabetic subjects showed either no
change (or an increase) in artery diameter in response to the postural change.
These

observations are consistent with either impaired or absent myogenic