Hyperreactivity of aortic smooth muscle to serotonin is related to the presence of atheroma in Watanabe heritable hyperlipidaemic rabbits

Abstract

Objective: The aim was to elucidate the contribution of atheromatous plaque to alterations of smooth muscle contraction to vasoconstrictive agents, by examining vasoreactivity of vascular smooth muscle from the thoracic aorta of 10-13 month old Watanabe heritable hyperlipidaemic rabbits. Methods: From the same vascular ring of the lower thoracic aorta, a pair of small medial smooth muscle strips was prepared from the sites beneath the atheroma (atherosclerotic medial muscle strip) and from those beneath the plaque-free intima (normal medial muscle strip), and isometric tension was measured. Results: Contractions to 118 mM KC1, histamine (30 nM to 10 μM), and noradrenaline (3 nM to 0.3 μM) were similar between atherosclerotic and the normal medial muscle strip. The ED₅₀ to serotonin was 49(SD 28) and 116(66) nM (p2+−free solution or in the presence of 10 μM H-7, an inhibitor of protein kinase C. After incubation with 0.1 μM phorbol 12,13-dibutyrate, an activator of protein kinase C, the isometric contractions induced by Ca²⁺ were significantly greater in atherosclerotic than in normal medial muscle strip. Conclusions: These results indicate that medial smooth muscle located beneath the atheroma is specifically hyperreactive to serotonin and that altered protein kinase C activity may explain in part the augmented response to serotonin. Cardiovascular Research 1993;27:2164-2169