Mechanism of coronary spasm was examined regarding endothelium-related relaxation and contraction produced by smooth muscle cells of spastic vessels isolated from Gottingen miniature pigs. In these pigs, coronary artery spasm was documented angiographically in vivo three months after endothelial denudation, and spastic and control segments of the coronary artery were suspended in organ chambers at their optimal length for generating tension. Applications of KCl (118 mM), acetylcholine (10-9 to 10-4 M), and PGF(2α) (10-8 to to 3 x 10-5 M) produced similar tension, at the respective doses, in both the spastic and control coronary arteries. During increasing concentrations of histamine (10-8 to 3 x 10-4 M; n = 14) and serotonin (10-9 to 10-5 M; n = 13), the maximum tension of the spastic vessel was 136 ± 6 and 97 ± 4%, respectively, of th tension produced by 118 mM KCl. That is significantly larger than seen in the control vessels: 98 ± 4 and 74 ± 4%, respectively. The ED50 to histamine and serotonin was also significantly less in the spastic vessels. After mechanical removal of the endothelium, the tension generated during the cumulative administration of histamine (n = 8) but not serotonin (n = 8) was larger in the spastic than the control vessels, thereby suggesting the presence of augmented responses of the smooth muscle to histamine in the spastic vessels. The increase in maximum tension after mechanical denudation was greater in the control than the spastic vessels in cases of histamine and serotonin. Endothelium-dependent relaxations due to serotonin (n = 5) and A23187 (n = 5) were tested under conditions of precontraction by PGF(2α) (10-5 M). The maximum relaxation induced by serotonin was 31 ± 4 and 67 ± 8% (p < 0.01) in the spastic and the control vessel, respectively. A23187 relaxed completely the spastic vessel, to a similar extent as seen in the control vessels; however, the ED50 of relaxation evoked by A23187 was 2.7 ± 0.6 x 10-8 and 6.3 ± 1.4 x 10-9 M (p < 0.01) in the spastic and the control vessels, respectively. Thus, both increased responsiveness of smooth muscle to histamine and impairment of endothelium-dependent relaxation to serotonin and to histamine may play an important role in the hypercontraction observed in coronary artery spasm in these miniature pigs.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine