Earley Scott, Resta Thomas C, Walker Benjimen R
Dept. of Cell Biology and Physiology, MSC08 4750, 1 Univ. of New Mexico, Albuquerque, NM 87131-0001, USA.
Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2677-86. doi: 10.1152/ajpheart.00016.2004. Epub 2004 Aug 19.
Communication between vascular smooth muscle (VSM) cells via low-resistance gap junctions may facilitate vascular function by synchronizing the contractile state of individual cells within the vessel wall. We hypothesized that inhibition of gap junctional communication would impair constrictor responses of mesenteric resistance arteries. Immunohistochemical experiments revealed positive staining for connexin 37 (Cx37) in both endothelium and smooth muscle of rat mesenteric arterioles, whereas connexin 43 (Cx43) immunoreactivity was not detected in the mesenteric vasculature. Administration of the gap junction inhibitory peptide Gap27, which targets Cx37 and Cx43, significantly diminished myogenic vasoconstriction (8.6 +/- 3.8% of passive diameter at 100 Torr) and changes in vessel wall intracellular [Ca2+] of mesenteric resistance arteries compared with vessels treated with either vehicle (physiological saline solution) (33.5 +/- 6.1%) or a control peptide (32.1 +/- 6.5%). Administration of 18alpha-glycyrrhetinic acid, structurally distinct from Gap27, also significantly attenuated myogenic constriction compared with its vehicle control (DMSO) (9.6 +/- 3.2% vs. 23.8 +/- 4.6%). In contrast, phenylephrine-induced vasoconstriction was not altered by gap junction blockers. Attenuated myogenic vasoconstriction resulting from inhibition of gap junctions persisted after disruption of the endothelium. In additional experiments, VSM cell membrane potential was recorded in mesenteric resistance arteries pressurized to 20 or 100 Torr. VSM membrane potential was depolarized at 100 Torr compared with 20 Torr. However, VSM cells in arteries treated with Gap27 were significantly hyperpolarized (-48.6 +/- 1.4 mV) at the higher pressure compared with vehicle (-41.4 +/- 1.5 mV) and Gap20-treated (-38.4 +/- 0.7 mV) vessels. Our findings suggest that inhibition of smooth muscle gap junctions attenuates pressure-induced VSM cell depolarization and myogenic vasoconstriction.
血管平滑肌（VSM）细胞之间通过低电阻缝隙连接进行的通讯，可能通过使血管壁内单个细胞的收缩状态同步来促进血管功能。我们推测，抑制缝隙连接通讯会损害肠系膜阻力动脉的收缩反应。免疫组织化学实验显示，大鼠肠系膜小动脉的内皮和平滑肌中连接蛋白37（Cx37）呈阳性染色，而在肠系膜脉管系统中未检测到连接蛋白43（Cx43）的免疫反应性。给予靶向Cx37和Cx43的缝隙连接抑制肽Gap27，与用载体（生理盐溶液）（33.5±6.1%）或对照肽（32.1±6.5%）处理的血管相比，显著减弱了肠系膜阻力动脉的肌源性血管收缩（在100 Torr时为被动直径的8.6±3.8%）和血管壁细胞内[Ca2+]的变化。给予结构不同于Gap27的18α-甘草次酸，与其载体对照（二甲基亚砜）相比，也显著减弱了肌源性收缩（9.6±3.2%对23.8±4.6%）。相比之下，苯肾上腺素诱导的血管收缩不受缝隙连接阻滞剂的影响。在内皮破坏后，由缝隙连接抑制引起的肌源性血管收缩减弱仍然存在。在另外的实验中，在加压至20或100 Torr的肠系膜阻力动脉中记录VSM细胞膜电位。与20 Torr相比，VSM膜电位在100 Torr时去极化。然而，与载体（-41.4±1.5 mV）和Gap20处理（-
