Department of Kinesiology, Kansas State University , Manhattan, Kansas.
Department of Anatomy and Physiology, Kansas State University , Manhattan, Kansas.
J Appl Physiol (1985). 2018 Jun 1;124(6):1558-1566. doi: 10.1152/japplphysiol.01022.2017. Epub 2018 Jan 25.
Premenopausal women express reduced blood pressure and risk of cardiovascular disease relative to age-matched men. This purportedly relates to elevated estrogen levels increasing nitric oxide synthase (NOS) activity and NO-mediated vasorelaxation. We tested the hypotheses that female rat skeletal muscle would: 1) evince a higher O delivery-to-utilization ratio (Q̇o/V̇o) during contractions; and 2) express greater modulation of Q̇o/V̇o with changes to NO bioavailability compared with male rats. The spinotrapezius muscle of Sprague-Dawley rats (females = 8, males = 8) was surgically exposed and electrically-stimulated (180 s, 1 Hz, 6 V). OxyphorG4 was injected into the muscle and phosphorescence quenching employed to determine the temporal profile of interstitial Po (Po, determined by Q̇o/V̇o). This was performed under three conditions: control (CON), 300 µM sodium nitroprusside (SNP; NO donor), and 1.5 mM N-nitro-l-arginine methyl ester (l-NAME; NOS blockade) superfusion. No sex differences were found for the Po kinetics parameters in CON or l-NAME ( P > 0.05), but females elicited a lower baseline following SNP (males 42 ± 3 vs. females 36 ± 2 mmHg, P < 0.05). Females had a lower ΔPo during contractions following SNP (males 22 ± 3 vs. females 17 ± 2 mmHg, P < 0.05), but there were no sex differences for the temporal response to contractions ( P > 0.05). The total NO effect (SNP minus l-NAME) on Po was not different between sexes. However, the spread across both conditions was shifted to a lower absolute range for females (reduced SNP baseline and greater reduction following l-NAME). These data support that females have a greater reliance on basal NO bioavailability and males have a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO. NEW & NOTEWORTHY Interstitial Po (Po; determined by O delivery-to-utilization matching) plays an important role for O flux into skeletal muscle. We show that both sexes regulate Po at similar levels at rest and during skeletal muscle contractions. However, modulating NO bioavailability exposes sex differences in this regulation with females potentially having a greater reliance on basal NO bioavailability and males having a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO.
绝经前女性的血压和心血管疾病风险低于同龄男性。这据称与雌激素水平升高有关，可增加一氧化氮合酶（NOS）活性和一氧化氮介导的血管舒张。我们检验了以下假设：1）与雄性大鼠相比，雌性大鼠的骨骼肌在收缩期间表现出更高的氧输送-利用比（Q̇o/V̇o）；2）与雄性大鼠相比，雌性大鼠的 Q̇o/V̇o 对一氧化氮生物利用度的变化有更大的调节作用。通过手术暴露 Sprague-Dawley 大鼠（雌性 8 只，雄性 8 只）的斜方肌，并进行电刺激（180 秒，1 Hz，6 V）。将氧磷灰石 G4 注入肌肉，并采用磷光猝灭法来确定间质 Po 的时间曲线（Po 通过 Q̇o/V̇o 确定）。在三种条件下进行此操作：对照（CON）、300 μM 硝普钠（SNP；NO 供体）和 1.5 mM N-硝基-L-精氨酸甲酯（l-NAME；NOS 阻断）灌流。在 CON 或 l-NAME 中，性别对 Po 动力学参数没有影响（P > 0.05），但雌性大鼠在 SNP 后基线更低（雄性 42 ± 3 对雌性 36 ± 2 mmHg，P < 0.05）。在 SNP 后，雌性大鼠的收缩期间 Po 下降幅度较低（雄性 22 ± 3 对雌性 17 ± 2 mmHg，P < 0.05），但对收缩的时间反应没有性别差异（P > 0.05）。Po 对 SNP 和 l-NAME 的总 NO 效应（SNP 减去 l-NAME）在性别之间没有差异。然而，女性的这种影响范围在两种情况下都向较低的绝对值范围转移（SNP 基线降低，l-NAME 后降低幅度更大）。这些数据支持这样的观点，即女性对基础一氧化氮生物利用度的依赖性更大，而男性对外源性一氧化氮的反应性更大，对内源性一氧化氮减少的反应性更小。新观点和重要发现 间质 Po（通过氧输送-利用匹配确定）在骨骼肌的氧通量中起着重要作用。我们表明，在休息和骨骼肌收缩期间，两性都以相似的水平调节 Po。然而，调节一氧化氮生物利用度会暴露出这种调节中的性别差异，女性可能对基础一氧化氮生物利用度的依赖性更大，而男性对外源性一氧化氮的反应性更大，对内源性一氧化氮减少的反应性更小。
