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Mechanisms of ergonovine-induced hyperconstriction of coronary artery after x-ray irradiation in pigs

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Abstract

Mechanisms of ergonovine-induced coronary hyperconstriction were examined in vivo and in vitro in miniature pigs. To provoke coronary hyperconstriction, the endothelium of a segment of a major branch of the left coronary artery was denuded in 19 Göttingen miniature pigs (4 to 6 months of age). In Group I (n=12), the denuded site of the coronary artery was selectively irradiated with 15 Gy of x-ray twice, 3 and 4 months after endothelial denudation. The remaining 7 pigs were not irradiated (Group II). The vasoconstrictive effect of intracoronary administration of ergonivine (1 to 1000 μg) was examined angiographically 3 months (just before irradiation in group I) and 5 months after denudation in the two groups. After the angiographical study, the vessels were isolated and isometric tensions were measured in an organ chamber. In the in vivo studies, ergonovineinduced vasoconstriction at the denuded and x-ray irradiated site in Group I was significantly greater than that at the control site or that at the denuded site in Group II. Pretreatments with serotonin receptor blockers (ketanserin or methysergide) significantly attenuated ergonovine-induced hyperconstriction, while an alpha-adrenergic receptor blocker (prazosin) did not (% inhibition; ketanserin 74±9%, p<0.01, methysergide 60±10%, p<0.01, prazosin 9±5%, NS). In the in vitro studies, ergonivine produced significantly greater tension at the denuded and x-ray irradiated site (Group I) than at the control site or at the denuded site (Group II). Ergonovine-induced endotheliumdependent relaxation was impaired at the denuded site in both groups to a similar extent. These results suggest that ergonovine-induced hyperconstriction at the denuded and x-ray irradiated coronary artery resulted mainly from the hyperreactivity of medial smooth muscle mediated by serotonin2 receptors.

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Authors and Affiliations

  1. Research Institute of Angiocardiology and Cardiovascular Clinic Faculty of Medicine, Kyushu University, 3-1-1, Maidashi Higashi-ku, 812, Fukuoka, Japan

    S. Egashira, W. Mitsuoka, H. Tagawa, T. Kuga, H. Tomoike, M. Nakamura & A. Takeshita M.D.

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  1. S. Egashira
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  2. W. Mitsuoka
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  3. H. Tagawa
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  4. T. Kuga
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  5. H. Tomoike
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  6. M. Nakamura
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  7. A. Takeshita M.D.
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Additional information

This work was supported in part by Grants-in-Aid for Scientific Research (63440037, 63870035, 63480231, 01624006) from the Ministry of Education, Science, and Culture, a Research Grant for Cardiovascular Disease (1S-1) from the Ministry of Health and Welfare, Japan, Grants-in-Aid for JSPS Fellowship for Japanese Junior Scientists and a grant from a geniatric disease.

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Egashira, S., Mitsuoka, W., Tagawa, H. et al. Mechanisms of ergonovine-induced hyperconstriction of coronary artery after x-ray irradiation in pigs. Basic Res Cardiol 90, 167–175 (1995). https://doi.org/10.1007/BF00789446

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  • DOI: https://doi.org/10.1007/BF00789446

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