Aim: AMP-activated protein kinase (AMPK) is recently proposed to participate in functional hyperemia. It is expressed in both endothelial and smooth muscle cells and may be activated by metabolic influences or by an increase of shear stress on the endothelium. Functional hyperemia is not manifested uniformly in different vascular beds, being most pronounced in skeletal muscles, moderate in intestine and negligible in skin. This study tested the hypothesis that the effects of AMPK activation will show similar pattern of tissue specificity.

Methods: The segments of small arteries from diaphragm (DA), mesentery (MA) and skin (SA) were isolated from male Wistar rats and mounted in wire myograph (DMT A/S). We studied the effects of AICAR (10⁻⁴ M) on vessel contraction to α₁-adrenoceptor agonist methoxamine. Similar experiments were done in the presence of NO-synthase inhibitor, L-NNA (10⁻⁴ M).

Results: 60-min incubation with AICAR greatly reduced the contractile responses of DA and MA, but did not change SA contraction. L-NNA treatment abolished the effect of AICAR in DA, while in MA the effect of AICAR was smaller but still evident.

Conclusions: AMPK activation results in diminished vasocontractile responses and this correlates with magnitude of functional hyperemia in different organs; the effect is absent in skin, where blood flow is mainly regulated by sympathetic influences. Endothelial NOS represents a major target of AMPK in DA. In MA AMPK may also reduce contraction of smooth muscle cells by changing their calcium homeostasis or reducing calcium sensitivity of contraction. Supported by RFBR (grant 12-04-01665-a).