Ishihata Akira, Sakai Miwako, Katano Yumi
Department of Physiology I, Yamagata University School of Medicine, 2-2-2, Iida-Nishi, Yamagata 990-2331, Japan.
Peptides. 2006 Jan;27(1):80-6. doi: 10.1016/j.peptides.2005.07.012. Epub 2005 Sep 12.
To elucidate whether aging influences the vascular contractile effect of urotensin II in rat thoracic aorta, and to evaluate the contribution of endothelial vasodilating substances in mediating the effect of urotensin II, the effect of urotensin II was examined in the vessels of young (2-3-month-old) and aged rat. Isolated rat aortic rings incubated in Krebs-Henseleit solution gassed with 95% O2/5% CO2 were stimulated with urotensin II, and the developed tension was measured. Urotensin II increased the developed tension, which was decreased by aging. In 2-3-months-old young aorta without endothelium, urotensin II (10(-10) to 10(-7)) elicited a concentration-dependent aortic contraction to the maximal response almost equivalent to high KCl-induced contraction (79.4+/-11.3% of KCl(max)). In the presence of endothelium, the urotensin II-induced vasoconstriction in young aorta was significantly attenuated to 33.3+/-4.6% of KCl(max). However, the contractile response was greater in the pretreatment with N(G)-nitro-L-arginine (L-NNA) (100 microM) (50.3+/-8.4% of KCl(max) in endothelial denuded aorta), suggesting the vasorelaxing role of endothelial nitric oxide. In 25-27-months-old aged rat aorta, the urotensin II-mediated contraction was remarkably decreased, both in the presence (6.3+/-2.0% of KCl(max)) and absence (11.7+/-3.0% of KCl(max)) of endothelium. A cyclooxygenase inhibitor, diclofenac (10 microM), did not have any effect on the urotensin II-induced contraction. These results suggest that urotensin II can induce vascular smooth muscle contraction in rat aorta, and there was an aging-related decline in the urotensin II-induced contraction. Endothelial production of nitric oxide in response to urotensin II but not cyclooxygenase metabolites such as prostacyclin may play a role in reducing the vascular constriction especially in young aorta.
为了阐明衰老是否影响尾加压素II对大鼠胸主动脉的血管收缩作用，并评估内皮舒张物质在介导尾加压素II作用中的贡献，我们检测了尾加压素II对年轻（2 - 3月龄）和老年大鼠血管的作用。将分离的大鼠主动脉环置于用95% O2/5% CO2 充气的Krebs - Henseleit溶液中孵育，用尾加压素II刺激，然后测量产生的张力。尾加压素II增加了产生的张力，而这种作用随衰老而减弱。在2 - 3月龄无内皮的年轻主动脉中，尾加压素II（10(-10)至10(-7)）引起浓度依赖性的主动脉收缩，最大反应几乎等同于高钾诱导的收缩（为KCl(max)的79.4±11.3%）。在内皮存在的情况下，尾加压素II诱导的年轻主动脉血管收缩显著减弱至KCl(max)的33.3±4.6%。然而，用N(G)-硝基-L-精氨酸（L-NNA，100 microM）预处理后收缩反应更大（内皮剥脱的主动脉中为KCl(max)的50.3±8.4%），提示内皮一氧化氮具有血管舒张作用。在25 - 27月龄老年大鼠主动脉中，无论内皮存在与否（分别为KCl(max)的6.3±2.0%和11.7±3.0%），尾加压素II介导的收缩均显著降低。一种环氧化酶抑制剂双氯芬酸（10 microM）对尾加压素II诱导的收缩没有任何影响。这些结果表明，尾加压素II可诱导大鼠主动脉血管平滑肌收缩，且尾加压素II诱导的收缩存在与衰老相关的下降。内皮产生的一氧化氮而非环氧化酶代谢产物如前列环素可能在减轻血管收缩中起作用，尤其是在年轻主动脉中。
