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Effect of aging on Rho‐kinase activity and vascular smooth muscle contractility in skeletal muscle resistance arteries
Author(s) -
Shin Song Yi,
Padgham Samuel,
Trache Andreea,
Woodman Christopher
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.705.8
Subject(s) - rho associated protein kinase , medicine , vascular smooth muscle , contractility , phenylephrine , vasoconstriction , rhoa , endocrinology , coronary arteries , vascular resistance , artery , smooth muscle , chemistry , biology , kinase , blood pressure , signal transduction , microbiology and biotechnology
Introduction Vasoconstrictor responses decline with age in resistance arteries. The mechanism for the decrement in constrictor function is not fully understood but has been proposed to involve signaling through the RhoA pathway. Objective We tested whether aging affects Rho kinase (ROCK) activity in aged resistance arteries. Methods Soleus feed arteries (SFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. Smooth muscle cells isolated from one group of SFA were lysed and ELISA assay was used for assessment of both ROCK isoforms, total ROCK 1 and 2, and their activity, phospho ROCK 1 and 2. A separate group of young and old SFA was cannulated with glass micropipettes for assessment of vasoconstrictor function. To isolate the role of smooth muscle in constrictor responses, endothelial cells were removed from cannulated arteries (denuded) by passing 5 ml of air through the lumen of the artery. Vasoconstrictor responses were assessed using increasing whole log doses of norepinephrine (NE; 10 −9 –10 −4 M), angiotensin II (Ang II; 10 −11 –10 −7 M), and phenylephrine (PE; 10 −9 –10 −4 M). Results Total ROCK 1 and ROCK 2 was similar in cells isolated from young and old SFA, whereas phospho‐ROCK 1 and phospho‐ROCK 2 were higher in cells isolated from old SFA relative to young arteries. Constrictor responses of denuded SFA to PE and Ang II were significantly impaired in old SFA relative to young SFA whereas constrictor responses to NE were preserved. In addition, presence of a ROCK inhibitor, Y 27632, reduced further the constrictor response to agonists. Conclusion The results of this study indicate that smooth muscle contractile function declines with age in SFA. Contractility regulation involves the ROCK pathway, but upregulation of ROCK activity in old arteries is not able to rescue the reduced contractility state in aging. Support or Funding Information AHA grant 0765043Y, AHA grant 4150031, and Sydney and J.L. Huffines Institute of Sports Medicine and Human Performance. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .