Figure 19.
Individual record showing the critical importance of time resolution and redundant vasodilator pathways in evaluating blood flow responses to pharmacological blockade in contracting skeletal muscles. In this forearm handgripping study (rhythmic contractions performed at 10% of maximal voluntary contraction for 20 min), addition of the KATP channel blocker glibenclamide after combined blockade of nitric oxide and prostaglandin synthesis (l-NAME + Ketorolac) caused an impressive but temporary reduction in blood flow to contracting forearm muscles. This was followed by a compensatory hyperemic response and return to steady-state values. One possible interpretation is that the blood flow response to contractions became more dependent on KATP channels during blockade of nitric oxide and prostaglandin synthesis. Thus it fell dramatically when glibenclamide was administered. This fall in flow then caused a mismatch between oxygen delivery and metabolism in the contracting muscles that evoked adenosine release. This caused a brief hyperemic response above the normal blood flow value associated with contractions and then a return toward the steady-state value seen before any intervention. These observations emphasize the need for rapid time course measurements of flow (beat-to-beat) when pharmacological blocking agents were given during contractions. Otherwise, it might be possible to miss effects of the drug on the pathway of interest. The individual responses seen in the larger experiment were variable, highlighting the possibility that there might be significant individual variability in the pathways normally recruited to evoke exercise hyperemia. [Adapted from Schrage et al. (415).]