In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 283, No. 4 ( 2002-10-01), p. H1271-H1281
Abstract:
The human saphenous vein (HSV) is the most widely used graft in coronary artery revascularization procedures and is susceptible to spasm perioperatively. The aim of this study is to elucidate the mechanism(s) of agonist-induced excitation-contraction coupling in this vessel. Isometric contraction experiments were combined with in situ smooth muscle intracellular Ca 2+ concentration ([Ca 2+ ] i ) imaging by confocal microscopy of intact undistended HSV segments during activation with phenylephrine (PE; 50 μM). Stimulation with PE produced a sustained contraction. Preincubation with 5 μM nifedipine, a blocker of the L-type voltage-operated Ca 2+ channel, or 50 μM SKF-96365, a blocker of both the voltage- and receptor-operated channels, reduced force generation by 25–30%. Ca 2+ imaging revealed that PE elicited only a transient rise in [Ca 2+ ] i , suggesting that Ca 2+ plays only a minor role. However, a requirement for basal Ca 2+ levels was demonstrated when PE contractions could not be maintained in Ca 2+ -free medium. In light of the transient Ca 2+ response, it appears that signals other than Ca 2+ must maintain the tonic contraction elicited by PE, such as those that sensitize the myofilaments to Ca 2+ . Application of HA-1077 (a Rho kinase inhibitor) at the peak of the contraction completely abolished the plateau phase of the response, whereas application of genistein (a tyrosine kinase inhibitor) reduced this phase by ∼50%. The foregoing results suggest that, whereas the transient Ca 2+ signal can contribute to the development of force, maintenance of the plateau phase of the PE contraction in the HSV is the result of myofilament Ca 2+ sensitization by Rho kinase and tyrosine phosphorylation. The elucidation of the mechanisms of excitation-contraction coupling in the HSV may be useful for the development of therapeutic strategies for the alleviation of vein graft spasm.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.01129.2001
Language:
English
Publisher:
American Physiological Society
Publication Date:
2002
detail.hit.zdb_id:
1477308-9
SSG:
12
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