To investigate the roles of ET in the regulation of peripheral vascular tone, we studied the effect of hyperlipidemia on vascular responsiveness in femoral arteries from rabbits with control groups of rabbits and test groups receiving a hyperlipidemic diet.

New Zealand Whites were anesthetized with pentobabital and killed by exsanguination from the femoral arteries. Arteries which were suspended on muscle chambers at their optimal length for contractile properties, were examined.

1. After 14-16 weeks of cholesterol-rich diet, plasma cholestrol and HDL levels were significantly higher in the hyperlipidemic rabbits than in the control rabbits. There was no significant difference in the triglyceride levels between the two groups. 2. The contractions caused by 60 mM KCI in the femoral arterial strips were significantly augmented (P<0.01). The contractile responses to phenylephrine or angiotensin II were also augmented, whereas 5-hydroxytryptamine or U46619- induced contraction was not affected by the hyperlipidemic diet. 3. In control rabbits, ET-1 and ET- 2 contracted femoral arteries in a concentraction-dependent manner, whereas sarafotoxin S6c and IRL 1620 had no effect. 4. Contractions caused by ET-1 and ET-2 were significantly diminished by hyperlipidemia. 5. ET-1-induced concentration-response curves were inhibited by BQ-610, but not affected by BQ-788 in the femoral arterial strips from control and hyperlipidemic rabbits.

These results suggest that ET is involved in the regulation of vascular tone in peripheral arteries and ETA receptor subtypes are mainly present in rabbit femoral arteries. Further more, ET-induced contraction is attenuated in hyperlipidemic rabbit, and the attenuated responses might be caused at least in part by the alteration of ET receptors (e.g. desensitization).