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

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 15Gy 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 ergonovine (1 to 1000 microgram) 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, ergonovine-induced 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, ergonovine 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 endothelium-dependent 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 serotonin receptors.