title: Vascular KATPchannels mitigate severe muscle O2delivery-utilization mismatch during contractions in chronic heart failure rats.
abstract: The vascular ATP-sensitive K+(KATP) channel is a mediator of skeletal muscle microvascular oxygenation (PO2mv) during contractions in health. We tested the hypothesis that KATPchannel function is preserved in chronic heart failure (CHF) and therefore its inhibition would reduce PO2mv and exacerbate the time taken to reach the PO2mv steady-state during contractions of the spinotrapezius muscle. Moreover, we hypothesized that subsequent KATPchannel activation would oppose the effects of this inhibition. Muscle PO2mv (phosphorescence quenching) was measured during 180s of 1-Hz twitch contractions (∼6V) under control, glibenclamide (GLI, KATPchannel antagonist; 5mg/kg) and pinacidil (PIN, KATPchannel agonist; 5mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (coronary artery ligation, left ventricular end-diastolic pressure: 18±1mmHg). GLI reduced baseline PO2mv (control: 28.3±0.9, GLI: 24.8±1.0mmHg, p<0.05), lowered mean PO2mv (average PO2mv during the overall time taken to reach the steady-state; control: 20.6±0.6, GLI: 17.6±0.3mmHg, p<0.05), and slowed the attainment of steady-state PO2mv (overall mean response time; control: 66.1±10.2, GLI: 93.6±7.8s, p<0.05). PIN opposed these effects on the baseline PO2mv, mean PO2mv and time to reach the steady-state PO2mv (p<0.05 for all vs. GLI). Inhibition of KATPchannels exacerbates the transient mismatch between muscle O2delivery and utilization in CHF rats and this effect is opposed by PIN. These data reveal that the KATPchannel constitutes one of the select few well-preserved mechanisms of skeletal muscle microvascular oxygenation control in CHF.
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA. Electronic address: clark40@k-state.edu.
authors.forename: Clark T
authors.initials: CT
authors.lastname: Holdsworth
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Ferguson
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Trenton D
authors.initials: TD
authors.lastname: Colburn
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Fees
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Jesse C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Hirai
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA; Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Poole
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506, USA; Department of Kinesiology, Kansas State University, Manhattan, KS, 66506, USA.
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Musch
mesh_terms: D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002908:Chronic Disease; D004195:Disease Models, Animal; D006333:Heart Failure / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000209:etiology / Q000628:therapy; D010100:Oxygen / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D054086:KATP Channels; D010100:Oxygen
keywords: Exercise hyperemia; Glibenclamide; Kinetics; Phosphorescence quenching; Pinacidil