Role of rat vascular KATP channels in setting microvascular oxygen pressure at the onset of contractions (1106.15)

Abstract

Effective blood‐muscle O2 flux demands a sufficient microvascular O2 driving pressure (PO2mv) which is set by the ratio of O2 delivery‐O2 utilization. Smooth muscle cell hyperpolarization contributes to exercise induced increases in skeletal muscle O2 delivery mediated, in part, by ATP‐sensitive K+ (KATP) channels. We hypothesized that KATP channel blockade via glibenclamide (GLI) would speed the fall of PO2mv following the onset of skeletal muscle contractions. Spinotrapezius PO2mv (phosphorescence quenching) was measured in 12 adult male Sprague Dawley rats at rest and during 180 s of 1 Hz twitch contractions (~7 V) under control (CON) and GLI (5 mg/kg) conditions. GLI increased mean arterial pressure (ΔCON: 2 ± 1, ΔGLI: 17 ± 4 mmHg, p < 0.05) and decreased heart rate (ΔCON: 3 ± 2, ΔGLI: ‐9 ± 3 bpm, p < 0.05) but did not change baseline PO2mv (CON: 34.0 ± 2.2, GLI: 33.7 ± 1.6 mmHg, p > 0.05). Following the onset of contractions the time constant, mean response time and contracting steady‐state PO2mv were not different between conditions (p > 0.05 for all). However, a clearly defined undershoot (p < 0.05) of the contracting steady‐state PO2mv was evident with GLI (8.0 ± 2.6 %) but not during CON (1.6 ± 1.1 %). Our data indicate that blockade of KATP channels does not impact PO2mv kinetics parameters during small muscle mass electrical stimulation, but can cause transient mismatch of O2 delivery‐O2 utilization prior to stabilizing at the contracting steady‐state PO2mv. This suggests that KATP channels contribute substantially to skeletal muscle microvascular function during the crucial rest to contraction transition and therefore have the potential to mediate skeletal muscle performance decrements evident in disease states.Grant Funding Source: Supported by AHA Midwest Affiliate 0750090Z, NIH HL‐108328