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Endothelium‐dependent modulation of cerebral artery myogenic tone by cyclopiazonic acid
Author(s) -
Tam Raymond,
Kerr Paul M,
Ondrusova Katarina,
Plane Frances
Publication year - 2012
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.26.1_supplement.853.3
Subject(s) - cyclopiazonic acid , apamin , cerebral arteries , serca , endothelium , myogenic contraction , thapsigargin , medicine , endothelium derived hyperpolarizing factor , endocrinology , vasodilation , chemistry , mesenteric arteries , nitric oxide , potassium channel , biology , artery , biochemistry , atpase , calcium , charybdotoxin , enzyme , smooth muscle
The myogenic response, the ability of cerebral arteries to constrict in response to increases in intra‐vascular pressure, is a key autoregulatory mechanism by which cerebral blood flow is maintained within narrow limits despite large changes in pressure. The endothelium modulates arterial diameter via the release of factors such as nitric oxide (NO) and by electrical coupling with smooth muscle cells. We hypothesized that disruption of endothelial intracellular Ca2+ stores will affect the cerebral artery myogenic response. In endothelium‐intact middle cerebral arteries, cyclopiazonic acid (CPA; 10 μM) and thapsigargin (500 nM), inhibitors of the sarcoplasmic Ca2+‐ATPase (SERCA), each inhibited development of myogenic tone, e.g. 80mmHg, tone development was reduced by 65.5 ± 6.0% (n=6). In endothelium‐denuded arteries, CPA and thapsigarin had no effect the myogenic response. In endothelium‐intact arteries, L‐NG‐nitroarginine methyl ester (100 mM), an inhibitor of NO synthase, did not affect the CPA‐induced loss of myogenic response but addition of apamin (50nM) and Tram‐34 (1 μM), inhibitors of endothelial small and intermediate conductance Ca2+‐activated potassium (KCa) channels, prevented the effect of CPA. These data indicate that inhibition of endothelial SERCA leads to the activation of KCa channels and loss of cerebral myogenic tone. Supported by HSFC.