H + Induces Arteriolar Vasodilation but Does Not Initiate a Conducted Response in Skeletal Muscle Microvasculature

Active hyperemia is the process where blood flow is recruited to a tissue to meet increased metabolic demand. Conducted responses are important to this process in order to direct blood flow to capillaries to feed active skeletal muscle fibres. A conducted response is a coordinated vasodilatory signal that travels from low to high branch order arterioles resulting in an increase in capillary perfusion. Conducted responses are hypothesized to be initiated by metabolic vasodilators ‐ byproducts of skeletal muscle metabolism‐ however, exactly which metabolites are involved remains unclear. Two vasodilatory metabolites of skeletal muscle metabolism are hydrogen ion (H + ) and carbon dioxide (CO 2 ). Both H + and CO 2 are interrelated through the bicarbonate (HCO 3 − ) buffer (HCO 3 − + H + <‐‐> H 2 CO 3 <‐‐> CO 2 + H 2 O) whereby H + reacts with HCO 3 − to produce CO 2 and CO 2 reacts in reverse to produce H + . Thus, it is difficult to study the individual effects of these metabolites. In order to separate them we used a Tris (amine) buffer to superfuse the preparation, to allow us to apply H + without changing CO 2 , thus allowing us to investigate the vasodilatory actions of H + independently. Using an in situ, intact hamster cremaster muscle model, H + was applied to the whole preparation through the superfusate or to a small region of a 2A arteriole (max. diameter approx. 40μm) via micropipette. Arteriolar diameter was recorded and analyzed offline. A range of H + concentrations (63.1 – 251.2 nMol; pH 7.2 – 6.6) applied to the entire preparation induced arteriolar vasodilation. The maximum change in diameter was 9.9±2.1μm, which was not a maximal dilation in the arteriole (only 71.1% of maximal diameter). Micropipette application of 251.2 nMol H + (pH 6.6), induced a local arteriolar vasodilation of 3.5±0.4μm however it did not elicit a significant vasodilation 1000μm upstream of the micropipette application site. These novel data demonstrate that H + is a local arteriolar vasodilator with a limited capacity to cause vasodilation and does not cause a conducted response, which is important in directing blood flow to active skeletal muscle cells during active hyperaemia. These data bring into question the importance of H + and changes in pH in the active hyperaemic response. Support or Funding Information NSERC, Canada