The present study was undertaken to investigate the effects of atherosclerotic progression on the responsiveness of rabbit aortae to ergonovine. For this purpose, we examined the contractile responses of isolated aortae from control rabbits (n=10) and Watanabe heritable hyperlipidemic rabbits (WHHL; n=16). WHHL rabbits were divided into three groups by their age: group I is composed of rabbits younger than 10 months, group II is from 10 to 22 months and group III is older than 22 months. Macroscopic and microscopic examination of aortae obtained from WHHL-I, II and III revealed that atherosclerotic changes were slight, moderate and severe, respectively. Aortae from control rabbits had no atheromatous lesions. Those helical strips were mounted in tissue baths filled with oxygenated Krebs solution for isometric tension recording.
The concentration-response curves for phenylephrine (10-8-3×10-5 M) in control and WHHL-II and III groups were almost identical with similar maximum contractions. The contractile responses to ergonovine in WHHL-I were almost the same as those in controls, while the concentrationresponse curve for ergonovine (10-10-3×10-5M) in WHHL-II was markedly shifted to the left with significantly low threshold concentration and ED50 value as compared with controls. The maximum contraction in WHHL-II was also increased. On the other hand, that for ergonovine in WHHL-III was similar to controls without any changes of ED50 values and maximum contractions. Only threshold concentration to ergonovine in WHHL-III was significantly lower than that in controls.
These findings suggest that the contractile responses of rabbit aortae to α1-adrenergic stimulation were not affected by the presence of atherosclerosis and by its progression, but those to ergonovine were affected. The contractile responses of aortae with slight atheromatous lesions were not changed as compared with controls, but aortae with moderate atherosclerosis were remarkably hyperreactive to ergonovine. In aortae with severe atherosclerosis, on the other hand, the hyperreactivity to ergonovine was markedly attenuated as compared with those with moderate atherosclerosis.
