HYPERREACTIVITY OF AORTIC SMOOTH-MUSCLE TO SEROTONIN IS RELATED TO THE PRESENCE OF ATHEROMA IN WATANABE HERITABLE HYPERLIPEMIC RABBITS

Objective: The aim was to elucidate the contribution of atheromatous p laque 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 ao rta, 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 KCl, histamine (30 nM to 10 mu M), and noradrenaline (3 nM to 0.3 mu M ) were similar between atherosclerotic and the normal medial muscle st rip. The ED(50) to serotonin was 49(SD 28) and 116(66) nM (p < 0.05, n = 7) and the maximum tension to serotonin was 125(29)% and 82(29)% of that induced by 118 mM KCl (p < 0.01, n = 7) in atherosclerotic and n ormal medial muscle strip, respectively. Serotonin specific hyperreact ivity of the atherosclerotic strip disappeared in Ca2+-free solution o r in the presence of 10 mu M H-7, an inhibitor of protein kinase C. Af ter incubation with 0.1 mu M phorbol 12,13-dibutyrate, an activator of protein kinase C, the isometric contractions induced by Ca2+ were sig nificantly greater in atherosclerotic than in normal medial muscle str ip. Conclusions: These results indicate that medial smooth muscle loca ted beneath the atheroma is specifically hyperreactive to serotonin an d that altered protein kinase C activity may explain in part the augme nted response to serotonin.