Regulation of Capillary Hemodynamics by KATP Channels in Resting Skeletal Muscle

Abstract

ATP‐sensitive potassium (KATP) channels have been implicated in the regulation of resting vascular smooth muscle membrane potential and tone. However, whether KATP channels modulate skeletal muscle microvascular hemodynamics at the capillary level (the primary site for blood‐myocyte O2 flux) is unknown. We tested the hypothesis that KATP channel inhibition would reduce the proportion of capillaries supporting continuous red blood cell flow and impair microvascular hemodynamics in perfused capillaries in resting skeletal muscle.METHODSIntravital microscopy was used to evaluate the in vivo spinotrapezius muscle microcirculation in healthy male Sprague‐Dawley rats (n=7; 347±19 g). Capillary lumen diameter (dcap) and red blood cell flux (fRBC), velocity (VRBC) and hematocrit (Hctcap) were assessed in the exteriorized spinotrapezius at physiological sarcomere lengths (2.7±0.1 μm). The percentage of red blood cell‐perfused capillaries was established as (no. of capillaries supporting RBC flow/total no. of visible capillaries per area)*100. Resting muscle capillary hemodynamics were examined under control (CON) and glibenclamide (GLI; KATP channel antagonist; 200 μM) superfusion conditions. Subsequent off‐line examination of the same microvascular fields within a given animal (i.e., CON vs. GLI) was conducted in real time via frame‐by‐frame techniques.RESULTSAs expected based on the topical drug delivery method, there were no differences in mean arterial pressure (CON: 104±5, GLI: 106±5 mmHg; P>0.05) or heart rate (CON: 316±26, GLI: 313±26 beats/min; P>0.05) between conditions. The percentage of capillaries supporting continuous red blood cell flow was reduced after GLI superfusion (CON: 90±2, GLI: 82±2%; P<0.05). In red blood cell‐perfused capillaries, GLI reduced fRBC (CON: 26±2, GLI: 19±2 cells/s; P<0.05) and VRBC (CON: 318±27; GLI: 215±23 μm/s; P<0.05) but not Hctcap (CON: 0.24±0.01, GLI: 0.24±0.01; P>0.05). Consistent with the well‐established arteriolar control of capillary blood flow in skeletal muscle, GLI‐induced alterations in microvascular hemodynamics occurred in the absence of changes in dcap between conditions (CON: 5.2±0.1, GLI: 5.3±0.1 μm; P>0.05).CONCLUSIONAlthough not affecting Hctcap, GLI reduced the number of capillaries supporting continuous red blood cell flow by approximately 9% thereby impairing muscle oxygen diffusing capacity (DO2). Within red blood cell‐perfused capillaries, GLI lowered both fRBC and VRBC by approximately 30% thus impairing perfusive microvascular O2 transport (i.e., capillary blood flow; Qcap). Given that fractional O2 extraction is determined by the DO2 to Qcap ratio (i.e., %O2 extraction = 1‐exp(−DO2/β*Qcap); where β is the slope of the O2 dissociation curve), greater impairments in Qcap relative to DO2 with GLI will necessitate increased O2 extraction to compensate for reduced blood flow and support basal oxidative metabolism. These data reveal that KATP channels are an important modulator of capillary hemodynamics therefore regulating transcapillary O2 flux in healthy resting skeletal muscle.Support or Funding InformationNIH HL‐2‐108328This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.