Ca2+-independent hypoxic vasorelaxation in porcine coronary artery

被引:11
作者
Gu, M [1 ]
Thorne, GD [1 ]
Wardle, RL [1 ]
Ishida, Y [1 ]
Paul, RJ [1 ]
机构
[1] Univ Cincinnati, Coll Med, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2005年 / 562卷 / 03期
关键词
D O I
10.1113/jphysiol.2004.073692
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
To demonstrate a Ca2+-independent component of hypoxic vasorelaxation and to investigate its mechanism, we utilized permeabilized porcine coronary arteries, in which [Ca2+] could be clamped. Arteries permeabilized with beta-escin developed maximum force in response to free Ca2+ (6.6 mum), concomitant with a parallel increase in myosin regulatory light chain phosphorylation (MRLC-P-i), from 0.183 +/- 0.023 to 0.353 +/- 0.019 MRLC-P-i (total light chain)(-1). Hypoxia resulted in a significant decrease in both force (-31.9 +/- 4.1% prior developed force) and MRLC-P-i (from 0.353 to 0.280 +/- 0.023), despite constant [Ca2+] buffered by EGTA (4 mm). Forces developed in response to Ca2+ (6.6 mum), Ca2+ (0.2 mum) + GTPgammaS (1 mm), or in the absence of Ca2+ after treatment with ATPgammaS (1 mm), were of similar magnitude. Hypoxia also relaxed GTPgammaS contractures but importantly, arteries could not be relaxed after treatment with ATPgammaS. Permeabilization with Triton X-100 for 60 min also abolished hypoxic relaxation. The blocking of hypoxic relaxation after ATPgammaS suggests that this Ca2+-independent mechanism(s) may operate through alteration of MRLC-P-i or of phosphorylation of the myosin binding subunit of myosin light chain phosphatase. Treatment with the Rho kinase inhibitor Y27632 (1 mum) relaxed GTPgammaS and Ca2+ contractures; but the latter required a higher concentration (10 mum) for consistent relaxation. Relaxations to N-2 and/or Y27632 averaged 35% and were not additive or dependent on order. Our data suggest that the GTP-mediated, Rho kinase-coupled pathway merits further investigation as a potential site of this novel, Ca2+-independent O-2-sensing mechanism. Importantly, these results unambiguously show that hypoxia-induced vasorelaxation can occur in permeabilized arteries where the Ca2+ is clamped at a constant value.
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收藏
页码:839 / 846
页数:8
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