Capillary hemodynamics and contracting skeletal muscle oxygen pressures in male rats with heart failure: Impact of soluble guanylyl cyclase activator.

Autor: Weber RE; Department of Kinesiology, Kansas State University, Manhattan, KS, USA. Electronic address: monaw@ksu.edu., Schulze KM; Department of Kinesiology, Kansas State University, Manhattan, KS, USA., Colburn TD; Department of Kinesiology, Kansas State University, Manhattan, KS, USA., Horn AG; Department of Kinesiology, Kansas State University, Manhattan, KS, USA., Hageman KS; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA., Ade CJ; Department of Kinesiology, Kansas State University, Manhattan, KS, USA., Hall SE; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA., Sandner P; Bayer AG, Cardiology Research, Wuppertal, Germany and Hannover Medical School, Department of Pharmacology, Hannover, Germany., Musch TI; Department of Kinesiology, Kansas State University, Manhattan, KS, USA; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA., Poole DC; Department of Kinesiology, Kansas State University, Manhattan, KS, USA; Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA.
Jazyk: angličtina
Zdroj: Nitric oxide : biology and chemistry [Nitric Oxide] 2022 Feb 01; Vol. 119, pp. 1-8. Date of Electronic Publication: 2021 Dec 04.
DOI: 10.1016/j.niox.2021.12.001
Abstrakt: In heart failure with reduced ejection fraction (HFrEF), nitric oxide-soluble guanylyl cyclase (sGC) pathway dysfunction impairs skeletal muscle arteriolar vasodilation and thus capillary hemodynamics, contributing to impaired oxygen uptake (V̇O 2 ) kinetics. Targeting this pathway with sGC activators offers a new treatment approach to HFrEF. We tested the hypotheses that sGC activator administration would increase the O 2 delivery (Q̇O 2 )-to-V̇O 2 ratio in the skeletal muscle interstitial space (PO 2 is) of HFrEF rats during twitch contractions due, in part, to increases in red blood cell (RBC) flux (f RBC ), velocity (V RBC ), and capillary hematocrit (Hct cap ). HFrEF was induced in male Sprague-Dawley rats via myocardial infarction. After 3 weeks, rats were treated with 0.3 mg/kg of the sGC activator BAY 60-2770 (HFrEF + BAY; n = 11) or solvent (HFrEF; n = 9) via gavage b.i.d for 5 days prior to phosphorescence quenching (PO 2 is, in contracting muscle) and intravital microscopy (resting) measurements in the spinotrapezius muscle. Intravital microscopy revealed higher f RBC (70 ± 9 vs 25 ± 8 RBC/s), V RBC (490 ± 43 vs 226 ± 35 μm/s), Hct cap (16 ± 1 vs 10 ± 1%) and a greater number of capillaries supporting flow (91 ± 3 vs 82 ± 3%) in HFrEF + BAY vs HFrEF (all P < 0.05). Additionally, PO 2 is was especially higher during 12-34s of contractions in HFrEF + BAY vs HFrEF (P < 0.05). Our findings suggest that sGC activators improved resting Q̇O 2 via increased f RBC , V RBC , and Hct cap allowing for better Q̇O 2 -to-V̇O 2 matching during the rest-contraction transient, supporting sGC activators as a potential therapeutic to target skeletal muscle vasomotor dysfunction in HFrEF.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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