In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 94, No. 2 ( 1996-07-15), p. 190-196
Abstract:
Background The intracellular mechanism for coronary artery spasm is still unknown. Since the protein kinase C (PKC)–mediated pathway and Ca 2+ release from sarcoplasmic reticulum (SR) are important intracellular mechanisms of vascular smooth muscle contraction, we examined the possible role of these two mechanisms in the pathogenesis of coronary spasm in our swine model in vivo. Methods and Results In 25 pigs, interleukin-1β (IL-1β) was applied chronically to the coronary arteries from the adventitia to induce an inflammatory/proliferative lesion. Two weeks after the operation, either intracoronary serotonin or histamine repeatedly induced coronary spasm at the IL-1β–treated site. At those spastic sites, phorbol-12,13-dibutyrate, a PKC-activating phorbol ester, also induced coronary spasm, which was blocked by pretreatment with the PKC inhibitors staurosporine and sphingosine. Serotonin- and histamine-induced coronary spasm was also significantly inhibited by pretreatment with staurosporine, sphingosine, or nifedipine (an L-type Ca 2+ channel antagonist) but not by ryanodine (an inhibitor of Ca 2+ -induced Ca 2+ release from SR) or thapsigargin (an inhibitor of Ca 2+ -ATPase of SR). Bay K 8644 (an L-type Ca 2+ channel agonist) also induced coronary spasm at the IL-1β–treated site, which was significantly inhibited by pretreatment with staurosporine, sphingosine, and nifedipine. In contrast, coronary vasoconstriction induced by prostaglandin F 2α was not affected by pretreatment with staurosporine or sphingosine but was significantly inhibited by pretreatment with ryanodine, thapsigargin, or nifedipine. Conclusions These results suggest that (1) PKC activation largely accounts for the serotonin- and histamine-induced coronary spasm; (2) at the spastic site, the calcium influx through L-type Ca 2+ channels may be augmented via the PKC-mediated pathway; and (3) the Ca 2+ release from the SR into the cytosol may not play a primary role in coronary spasm.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/01.CIR.94.2.190
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1996
detail.hit.zdb_id:
1466401-X
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