Effects of chronic heart failure on neuronal nitric oxide synthase-mediated control of microvascular O2 pressure in contracting rat skeletal muscle.
Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of the skeletal muscle microvascular O(2) delivery/V(O(2)) ratio (which sets the microvascular O(2) pressure, PO(2)mv). Given the pervasiveness of endothelial dysfunction in CHF, this NO-mediated dysregulation is attributed generally to eNOS. It is unknown whether nNOS-mediated PO(2)mv regulation is altered in CHF. We tested the hypothesis that CHF impairs nNOS-mediated PO(2)mv control. In healthy and CHF (left ventricular end diastolic pressure (LVEDP): 6 ± 1 versus 14 ± 1 mmHg, respectively, P < 0.05) rats spinotrapezius muscle blood flow (radiolabelled microspheres), PO(2)mv (phosphorescence quenching), and V(O(2)) (Fick calculation) were measured before and after 0.56 mg kg(-1)i.a. of the selective nNOS inhibitor S-methyl-l-thiocitrulline (SMTC). In healthy rats, SMTC increased baseline PO(2)mv (


METHODS
29.7 ± 1.4, SMTC: 34.4 ± 1.9 mmHg, P < 0.05) by reducing V(O(2)) (↓20%) without any effect on blood flow and speeded the mean response time (MRT, time to reach 63% of the overall kinetics response,


METHODS
24.2 ± 2.0, SMTC: 18.5 ± 1.3 s, P < 0.05). In CHF rats, SMTC did not alter baseline PO(2)mv (


METHODS
25.7 ± 1.6, SMTC: 28.6 ± 2.1 mmHg, P > 0.05), V(O(2)) at rest, or the MRT (CONTROL: 22.8 ± 2.6, SMTC: 21.3 ± 3.0 s, P > 0.05). During the contracting steady-state, SMTC reduced blood flow (↓15%) and V(O(2)) (↓15%) in healthy rats such that PO(2)mv was unaltered (


METHODS
19.8 ± 1.7, SMTC: 20.7 ± 1.8 mmHg, P > 0.05). In marked contrast, in CHF rats SMTC did not change contracting steady-state blood flow, V(O(2)), or PO(2)mv (


METHODS
17.0 ± 1.4, SMTC: 17.7 ± 1.8 mmHg, P > 0.05). nNOS-mediated control of skeletal muscle microvascular function is compromised in CHF versus healthy rats. Treatments designed to ameliorate microvascular dysfunction in CHF may benefit by targeting improvements in nNOS function.
Department of Anatomy and Physiology, Kansas State University, Manhattan, KS 66506-5802, USA.
Steven W
SW
Copp
Daniel M
DM
Hirai
Scott K
SK
Ferguson
Clark T
CT
Holdsworth
Timothy I
TI
Musch
David C
DC
Poole
D000818:Animals; D001794:Blood Pressure; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology*; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D010100:Oxygen / Q000502:physiology; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow
D052248:Nitric Oxide Synthase Type I; D010100:Oxygen