Enhanced responsiveness of smooth muscle, impaired endothelium-dependent relaxation and the genesis of coronary spasm

Hitonobu Tomoike, Kensuke Egashira, Yusuke Yamamoto, Motoomi Nakamura

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Abstract

Pathophysiology and genesis of coronary artery spasm were examined in vivo and in vitro in Gottingen miniature pigs. Five of 36 consecutive pigs before endothelial denudation showed evidence of regional hyperconstriction after intracoronary administration of histamine (group 1). Histologic examination revealed intimal thickening along the spastic site. Because 5 pigs died during endothelial denudation, cholesterol feeding was randomly assigned to 13 of the remaining 26 pigs (group 2) and others were fed a regular low cholesterol diet (group 3) for 3 months. Regional coronary hyperconstriction was also evident after intracoronary administration of histamine at the site of denudation, and the degree of constriction was 78 ± 3 and 74 ± 4% in groups 2 and 3, respectively. Because the intimal thickening was confirmed at the site of spasm in groups 2 and 3, spontaneous as well as denudation-induced intimal thickening accompanied the enhanced responsiveness to histamine, irrespective of the level of serum cholesterol. However, the role of geometry on histamine-induced luminal narrowing was only 6% and was not physiologically significant. Augmented responses of the coronary artery to histamine, but not to phenylephrine or potassium chloride were reproduced in the nonbeating isolated heart preparations perfused at 90 mm Hg with oxygenated Krebs-Henseleit solution, and the degree and location of in vitro hyperconstriction were similar to that in vivo and were not attenuated after pretreatment with the nerve transmitter blockers, guanethidine (3 × 10-6 M), atropine (10-6 M) and tetrodotoxin (3 × 10-7 M). Accordingly, spasm can be provoked without the influence of blood constituents and neural factors. Hyperconstriction was markedly attenuated by H1 receptor blocker or by perfusates without calcium ion, which suggests the enhanced calcium2+ influx through the activation of H1 receptor. Circumferential vascular strips were isolated from the spastic and normal vessels, and cumulative dose-response relations showed increased sensitivity and tension to histamine, but not to prostaglandin F and phenylephrine at the spastic segments. Changes in tension after removal of the endothelium were larger in the control than in the spastic segments at 10 -4 M histamine. Thus, both histamine-induced hypercontraction and impaired endothelium-dependent relaxation played an important role in the genesis of coronary spasm.

Original languageEnglish
Pages (from-to)E33-E39
JournalThe American Journal of Cardiology
Volume63
Issue number10
DOIs
Publication statusPublished - Mar 7 1989
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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