Department of Biomedical Sciences Human Health, University of Guelph, ANNU Bldg, Room 350, Guelph, Ontario, Canada N1G 2W1.
J Endocrinol. 2013 Jul 1;218(2):179-91. doi: 10.1530/JOE-13-0115. Print 2013.
Relaxin produces a sustained decrease in total peripheral resistance, but the effects of relaxin on skeletal muscle arterioles, an important contributor to systemic resistance, are unknown. Using the intact, blood-perfused hamster cremaster muscle preparation in situ, we tested the effects of relaxin on skeletal muscle arteriolar microvasculature by applying 10(-10) M relaxin to second-, third- and fourth-order arterioles and capillaries. The mechanisms responsible for relaxin-induced dilations were explored by applying 10(-10) M relaxin to second-order arterioles in the presence of 10(-5) M N(G)-nitro-l-arginine methyl ester (l-NAME, nitric oxide (NO) synthase inhibitor), 10(-5) M glibenclamide (GLIB, ATP-dependent potassium (K(+)) channel inhibitor), 10(-3) M tetraethylammonium (TEA) or 10(-7) M iberiotoxin (IBTX, calcium-associated K(+) channel inhibitor). Relaxin caused second- (peak change in diameter: 8.3 ± 1.7 μm) and third (4.5 ± 1.1 μm)-order arterioles to vasodilate transiently while fourth-order arterioles did not (0.01 ± 0.04 μm). Relaxin-induced vasodilations were significantly inhibited by l-NAME, GLIB, TEA and IBTX. Relaxin stimulated capillaries to induce a vasodilation in upstream fourth-order arterioles (2.1 ± 0.3 μm), indicating that relaxin can induce conducted responses vasodilation that travels through blood vessel walls via gap junctions. We confirmed gap junction involvement by showing that gap junction uncouplers (18-β-glycyrrhetinic acid (40 × 10(-6) M) or 0.07% halothane) inhibited upstream vasodilations to localised relaxin stimulation of second-order arterioles. Therefore, relaxin produces transient NO- and K(+) channel-dependent vasodilations in skeletal muscle arterioles and stimulates capillaries to initiate conducted responses. The transient nature of the arteriolar dilation brings into question the role of skeletal muscle vascular beds in generating the sustained systemic haemodynamic effects induced by relaxin.
松弛素会持续降低总外周阻力，但松弛素对骨骼肌小动脉的影响（全身阻力的重要贡献者）尚不清楚。我们使用完整的、血液灌注的仓鼠提睾肌原位制备物，通过将 10(-10)M 松弛素应用于第二、三和四级小动脉和毛细血管，来测试松弛素对骨骼肌小动脉微血管的影响。通过将 10(-10)M 松弛素应用于二级小动脉，在存在 10(-5)M N(G)-硝基-l-精氨酸甲酯 (l-NAME，一氧化氮 (NO) 合酶抑制剂)、10(-5)M 格列本脲 (GLIB，三磷酸腺苷 (ATP) 依赖性钾 (K(+)) 通道抑制剂)、10(-3)M 四乙铵 (TEA) 或 10(-7)M iberiotoxin (IBTX，钙相关 K(+)) 通道抑制剂），探索了松弛素诱导扩张的机制。松弛素引起二级（直径峰值变化：8.3 ± 1.7μm）和三级（4.5 ± 1.1μm）小动脉短暂扩张，而四级小动脉则没有（0.01 ± 0.04μm）。松弛素诱导的血管扩张明显被 l-NAME、GLIB、TEA 和 IBTX 抑制。松弛素刺激毛细血管引起上游四级小动脉的血管扩张（2.1 ± 0.3μm），表明松弛素可以诱导通过缝隙连接在血管壁内传播的扩血管反应。我们通过显示缝隙连接解偶联剂（18-β-甘草次酸（40×10(-6)M）或 0.07% 氟烷）抑制局部二级小动脉松弛素刺激引起的上游血管扩张，证实了缝隙连接的参与。因此，松弛素在骨骼肌小动脉中产生短暂的 NO 和 K(+) 通道依赖性血管扩张，并刺激毛细血管引发扩血管反应。小动脉扩张的短暂性质使骨骼肌血管床在产生松弛素引起的持续全身血液动力学效应中的作用受到质疑。
