Department of Kinesiology, William and Mary, Williamsburg, Virginia, United States.
Am J Physiol Heart Circ Physiol. 2024 Jan 1;326(1):H190-H202. doi: 10.1152/ajpheart.00170.2023. Epub 2023 Nov 3.
Myoendothelial feedback (MEF), the endothelium-dependent vasodilation following sympathetic vasoconstriction (mediated by smooth muscle to endothelium gap junction communication), has been well studied in resistance arteries of males, but not females. We hypothesized that MEF responses would be similar between the sexes, but different in the relative contribution of the underlying nitric oxide and hyperpolarization mechanisms, given that these mechanisms differ between the sexes in agonist-induced endothelium-dependent dilation. We measured MEF responses (diameter changes) of male and female first- to second-order mouse mesenteric arteries to phenylephrine (10 µM) over 30 min using isolated pressure myography ± blinded inhibition of nitric oxide synthase (NOS) using -nitro-l-arginine methyl ester (l-NAME; 0.1-1.0 mM), hyperpolarization using 35 mM KCl, or transient receptor potential vanilloid 4 (TRPV4) channels using GSK219 (0.1-1.0 µM) or RN-1734 (30 µM). MEF was similar [%dilation (means ± SE): males = 26.7 ± 2.0 and females = 26.1 ± 1.9 at 15 min] and significantly inhibited by l-NAME (1.0 mM) at 15 min [%dilation (means ± SE): males = 8.2 ± 3.3, < 0.01; females = 6.8 ± 1.9, < 0.001] and over time ( < 0.01) in both sexes. l-NAME (0.1 mM) + 35 mM KCl nearly eliminated MEF in both sexes ( < 0.001-0.0001). Activation of TRPV4 with GSK101 (0.1-10 µM) induced similar dilation between the sexes. Inhibition of TRPV4, which is reportedly involved in the hyperpolarization mechanism, did not inhibit MEF in either sex. Similar expression of eNOS was found between the sexes with Western blot. Thus, MEF is prominent and similar in murine first- and second-order mesenteric resistance arteries of both sexes, and reliant primarily on NOS and secondarily on hyperpolarization, but not TRPV4. We found that female mesenteric resistance arteries have similar postconstriction dilatory responses (i.e., myoendothelial feedback) to a sympathetic neurotransmitter analog as male arteries. Both sexes use nitric oxide synthase (NOS) and hyperpolarization, but not TRPV4, in this response. Moreover, the key protein involved in this pathway (eNOS) is similarly expressed in these arteries between the sexes. These similarities are surprising given that agonist-induced endothelium-dependent dilatory mechanisms differ in these arteries between the sexes.
肌内皮反馈（MEF）是指交感神经缩血管作用后内皮依赖性血管舒张（由平滑肌到内皮的缝隙连接通讯介导），在雄性阻力血管中已有很好的研究，但在雌性中则没有。我们假设 MEF 反应在两性之间相似，但在潜在的一氧化氮和超极化机制的相对贡献上有所不同，因为这些机制在激动剂诱导的内皮依赖性舒张中存在性别差异。我们使用离体压力测微法测量了雄性和雌性第一至第二级小鼠肠系膜动脉对苯肾上腺素（10 μM）的 MEF 反应（直径变化），持续 30 分钟，同时使用 -硝基-L-精氨酸甲酯（l-NAME；0.1-1.0 mM）抑制一氧化氮合酶（NOS），使用 35 mM KCl 抑制超极化，或使用 GSK219（0.1-1.0 μM）或 RN-1734（30 μM）抑制瞬时受体电位香草酸 4（TRPV4）通道。MEF 相似[（平均 ± SE）：雄性=26.7±2.0，雌性=26.1±1.9，在 15 分钟]，并在 15 分钟时被 l-NAME（1.0 mM）显著抑制[（平均 ± SE）：雄性=8.2±3.3， < 0.01；雌性=6.8±1.9， < 0.001]和随时间推移（ < 0.01）在两性中都受到抑制。l-NAME（0.1 mM）+35 mM KCl 几乎消除了两性中的 MEF（ < 0.001-0.0001）。TRPV4 的激活用 GSK101（0.1-10 μM）在两性中诱导相似的舒张。抑制 TRPV4，据报道其参与超极化机制，但在两性中均不抑制 MEF。Western blot 显示两性之间的内皮型一氧化氮合酶（eNOS）表达相似。因此，雄性和雌性的第一和第二级肠系膜阻力动脉均存在明显且相似的 MEF，主要依赖于 NOS，其次是超极化，但不依赖于 TRPV4。我们发现，雌性肠系膜阻力动脉对交感神经递质类似物的后收缩舒张反应（即肌内皮反馈）与雄性动脉相似。两性都在这个反应中使用一氧化氮合酶（NOS）和超极化，但不使用 TRPV4。此外，这个通路中的关键蛋白（eNOS）在两性之间的这些动脉中表达相似。这些相似性令人惊讶，因为在这些动脉中，激动剂诱导的内皮依赖性舒张机制在两性之间存在差异。
