Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

Abstract

This study was undertaken to examine the response to ergonovine, an agent used to provoke spastic constriction of large epicardial coronary arteries, to elucidate the responsible underlying mechanism, and to determine the impact of endogenous hyperlipidemia on contractile properties of isolated vessels from different beds. The isolated arteries from both control and Watanabe hereditary hyperlipidemic rabbits (WHHL rabbits) were suspended for recording isometric force in oxygenated Krebs buffer and exposed to agonists and antagonists. In atherosclerotic aortas from WHHL rabbits, the concentration-response relations for ergonovine and serotonin exhibited a marked leftward shift with significantly depressed constrictor threshold concentration and lowered one-half maximally effective concentration values. In coronary arteries with no atherosclerotic lesions detectable macroscopically from WHHL rabbits, the concentration-response relations showed a leftward shift for ergonovine but not serotonin. Coronary contraction evoked by ergonovine was remarkably inhibited by 0.1 microM cyproheptadine and 0.3 microM methysergide, serotonergic antagonists, in both groups. alpha-Adrenergic blockade with 0.1 microM prazosin was effective in inhibiting ergonovine-induced contraction of aortas from control rabbits, but not that of atherosclerotic ones. The constrictor response to ergonovine of atherosclerotic aortas was inhibited by cyproheptadine. The responsiveness to ergonovine of both carotid and femoral arteries from WHHL rabbits with no sclerotic lesions, which was suppressed by prazosin was not different from that of control rabbits. In contrast, the concentration-response relations for phenylephrine in the four different types of arteries did not differ appreciably between the two groups, and the constrictor responses to 20 mM KCl were virtually identical. Thus, aortas and coronary arteries exposed to endogenous hyperlipidemia appear to be hyperreactive to ergonovine mediated by a serotonergic mechanism.