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Nitric Oxide (NO) Bioavailability Underlies Muscle Microvascular O 2 Delivery/Utilization Imbalance in Chronic Heart Failure (CHF) Rats
Author(s) -
Hirai Daniel M,
Copp Steven W,
Ferreira Leonardo F,
Musch Timothy I,
Poole David C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.948.12
Subject(s) - heart failure , bioavailability , medicine , preload , nitric oxide , cardiology , endocrinology , hemodynamics , pharmacology
NO bioavailability has been implicated in the muscle microvascular dysfunction of CHF at rest and during contractions. PURPOSE To test the hypothesis that differences in the O 2 delivery/utilization balance, which sets the microvascular O 2 partial pressure (PO 2 mv ), between control (C) and severe CHF rats following the onset of contractions are due substantially to NO reduction. METHODS PO 2 mv was measured via phosphorescence quenching in the spinotrapezius muscle of 6 C and 4 CHF rats (male Sprague‐Dawley, 7‐10 wk post‐myocardial infarction, LVEDP 35 + 2 mmHg). Separate electrically‐induced contraction bouts (1 Hz) were performed with superfusion of SNP (300 μmol), Krebs‐Henseleit buffer (KH), and L‐NAME (1.5 mmol). The area under the PO 2 mv profile (PO 2AREA ) was calculated from 0‐60 s of each bout (expressed below as mmHg·s/min). RESULTS For KH, C had a greater ( P < 0.05) PO 2AREA (1042 ± 62) than CHF (721 ± 141). SNP increased PO 2AREA (C: 1371 ± 59, CHF: 1263 ± 97, P > 0.05) whereas L‐NAME reduced PO 2AREA (C: 613 ± 74, CHF: 416 ± 70, P > 0.05) to equivalent values in C and CHF rats. CONCLUSIONS This demonstrates, for the first time, that the impaired muscle microvascular O 2 delivery/utilization balance in CHF is eliminated by increasing (SNP) or removing (L‐NAME) NO bioavailability suggesting that the dysfunctional CHF PO 2 mv profile results principally from endogenous NO alterations. AHA, Heartland Affiliate 0750090Z