Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury

Kensuke Egashira, Hitonobu Tomoike, Yasuo Hayashi, Akira Yamada, Motoomi Nakamura, Akira Takeshita

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4±2.3% and 3.8±0.8% (p<0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1±1.1% to 2.7±1.0% (p<0.01) at the denuded site and from 4.2±0.6% to 0.8±0.3% (p<0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimai thickening and regenerated endothelium in the denuded site. These results suggest that the ergonovine-induced coronary hyperconstriction in our conscious canine model may be mediated by activation of serotonergic receptors with a subsequent increase in calcium influx into vascular smooth muscle cells.

Original languageEnglish
Pages (from-to)435-442
Number of pages8
JournalCirculation research
Volume71
Issue number2
DOIs
Publication statusPublished - Aug 1992

Fingerprint

Ergonovine
Coronary Vessels
Dogs
Wounds and Injuries
Constriction
Dilatation
Methysergide
Ketanserin
Diltiazem
Prazosin
Phenylephrine
Vasoconstriction
Vascular Smooth Muscle
Indomethacin
Smooth Muscle Myocytes
Endothelium
Canidae
Calcium

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury. / Egashira, Kensuke; Tomoike, Hitonobu; Hayashi, Yasuo; Yamada, Akira; Nakamura, Motoomi; Takeshita, Akira.

In: Circulation research, Vol. 71, No. 2, 08.1992, p. 435-442.

Research output: Contribution to journalArticle

Egashira, Kensuke ; Tomoike, Hitonobu ; Hayashi, Yasuo ; Yamada, Akira ; Nakamura, Motoomi ; Takeshita, Akira. / Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury. In: Circulation research. 1992 ; Vol. 71, No. 2. pp. 435-442.
@article{22020f1867414162bab59979ab64f493,
title = "Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury",
abstract = "This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4±2.3{\%} and 3.8±0.8{\%} (p<0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1±1.1{\%} to 2.7±1.0{\%} (p<0.01) at the denuded site and from 4.2±0.6{\%} to 0.8±0.3{\%} (p<0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimai thickening and regenerated endothelium in the denuded site. These results suggest that the ergonovine-induced coronary hyperconstriction in our conscious canine model may be mediated by activation of serotonergic receptors with a subsequent increase in calcium influx into vascular smooth muscle cells.",
author = "Kensuke Egashira and Hitonobu Tomoike and Yasuo Hayashi and Akira Yamada and Motoomi Nakamura and Akira Takeshita",
year = "1992",
month = "8",
doi = "10.1161/01.RES.71.2.435",
language = "English",
volume = "71",
pages = "435--442",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Mechanism of ergonovine-induced hyperconstriction of the large epicardial coronary artery in conscious dogs a month after arterial injury

AU - Egashira, Kensuke

AU - Tomoike, Hitonobu

AU - Hayashi, Yasuo

AU - Yamada, Akira

AU - Nakamura, Motoomi

AU - Takeshita, Akira

PY - 1992/8

Y1 - 1992/8

N2 - This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4±2.3% and 3.8±0.8% (p<0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1±1.1% to 2.7±1.0% (p<0.01) at the denuded site and from 4.2±0.6% to 0.8±0.3% (p<0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimai thickening and regenerated endothelium in the denuded site. These results suggest that the ergonovine-induced coronary hyperconstriction in our conscious canine model may be mediated by activation of serotonergic receptors with a subsequent increase in calcium influx into vascular smooth muscle cells.

AB - This study investigated the mechanism of ergonovine-induced hyperconstriction of coronary artery in conscious dogs that had undergone endothelial denudation one month earlier. The diameter of the large epicardial coronary artery was continuously measured by a sonomicrometer in 12 dogs in which two pairs of 10-MHz piezoelectric crystals had been surgically implanted at the denuded and nondenuded sites of coronary arteries. A month after the endothelial denudation, intravenous ergonovine (0.01, 0.1, 0.3, and 1.0 mg) produced transient dilation followed by dose-dependent constriction. The degrees of dilation were comparable between the denuded and nondenuded sites. The magnitudes of constriction induced by ergonovine were significantly larger in the denuded site than in the nondenuded site: the percent reductions in diameter evoked with 0.3 mg ergonovine were 14.4±2.3% and 3.8±0.8% (p<0.01) at the denuded and nondenuded sites, respectively. The magnitudes of constriction induced by intravenous phenylephrine (0.02, 0.06, and 0.2 mg) were comparable in the denuded and nondenuded sites. Methysergide (a nonselective serotonergic blocker) in a dose of 0.5 mg/kg significantly inhibited vasoconstriction induced by ergonovine (0.3 mg) from 13.1±1.1% to 2.7±1.0% (p<0.01) at the denuded site and from 4.2±0.6% to 0.8±0.3% (p<0.05) at the nondenuded site. Diltiazem (1.0 mg/kg) selectively inhibited the ergonovine-induced hyperconstriction. Ketanserin (0.5 mg/kg), prazosin (1.0 mg/kg), or indomethacin (5.0 mg/kg) did not prevent the ergonovine-induced hyperconstriction. Histological study revealed intimai thickening and regenerated endothelium in the denuded site. These results suggest that the ergonovine-induced coronary hyperconstriction in our conscious canine model may be mediated by activation of serotonergic receptors with a subsequent increase in calcium influx into vascular smooth muscle cells.

UR - http://www.scopus.com/inward/record.url?scp=0026633832&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026633832&partnerID=8YFLogxK

U2 - 10.1161/01.RES.71.2.435

DO - 10.1161/01.RES.71.2.435

M3 - Article

C2 - 1628398

AN - SCOPUS:0026633832

VL - 71

SP - 435

EP - 442

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 2

ER -