Effects of a high-cholesterol diet on vascular and endothelial function in rat aorta

We have examined the effects of high cholesterol (1%) or normal diet for 8 weeks on vascular and endothelial responsiveness of rat aorta. The cholesterol diet produced a small but significant elevation of plasma cholesterol levels (vehicle: 0.95 +/- 0.13 mmol/l, n = 11; cholesterol fed; 1.40 +/- o.12 mmol/1, n = 14; p < 0.05). There were significant differences between control and high cholesterol groups in the contractile response to noradrenaline in rat aortic rings, both in terms of maximum response and potency. Both the potency of noradrenaline (NA) (pD2 values; vehicle diet: 7.84 +/- 0.08; cholesterol diet: 8.27 +/- 0.09; p < 0.01) and the maximum response (vehicle diet: 0.78 +/- 0.05 g; cholesterol diet: 0.95 +/- 0.06 g; p < 0.05) were significantly greater in the high-cholesterol group. There were no significant differences between control and high cholesterol groups in endothelium-independent relaxations to sodium nitroprusside (SNP). When responses were correlated with plasma cholesterol levels, there was a significant negative correlation with maximum endothelium-dependent relaxation to ACh (r = 0.53, n = 16, p < 0.05), so that the maximum relaxation decreased with increasing plasma levels of cholesterol. There were no significant correlations between cholesterol levels and endothelium-independent relaxation to SNP or between cholesterol levels and vascular contractions to NA. In conclusion, cholesterol-fed normal Wistar rats show functional changes in vascular responsiveness even with a relatively small elevation of plasma cholesterol levels.