EFFECTS OF HYPERLIPIDEMIA ON THE VASCULAR REACTIVITY IN THE WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

We studied the effects of hyperlipidemia on the vascular responsivenes s in aortas isolated from control rats and rats receiving a high chole sterol-high fat (HC-HF) diet (1% cholesterol and 20% olive oil). The t otal plasma cholesterol, very low density lipoprotein (VLDL)-, low den sity lipoprotein (LDL)-cholesterol, VLDL-, LDL-, high density lipoprot ein (HDL)-triglyceride levels were markedly elevated in HC-HF chow fed Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) compared to the respective normal chow fed control rats. The increase in plasm a cholesterol and triglyceride levels were time-dependent. Higher leve ls of cholesterol and triglyceride were observed in SHR compared to WK Y. In the aortic arches and abdominal aortas obtained from the SHR and WKY fed the HC-HF chow for 8 weeks, evoked intimal lesions were more pronounced than those noted after 4 weeks of HC-HF chow fed. The aorti c arches of SHR and WKY were significantly more affected by the intima l lesion (surface area damage and fatty streak formation) than the abd ominal aortas of the respective rat strain. The damage of surface area and thickness of fatty streaks were significantly augmented with the period the rats were fed the HC-HF diet. In the denuded aortic arches of the WKY and of rats receiving HC-HF diet for 8 weeks, significantly attenuated ED(50) values and augmented maximal responses for phenylep hrine (0.01-30 mu M)-induced contraction were obtained. Endothelium-de pendent relaxation to acetylcholine was abolished, while endothelium-i ndependent relaxation to nitroprusside was well preserved in the denud ed aortic arches and abdominal aortas of the WKY, SHR rats with or wit hout 8 week HC-HF diet. We conclude from these studies that in the iso lated aortas from hyperlipidemic WKY and SHR: (1) the contractions ind uced by phenylephrine are augmented, (2) the endothelium-dependent rel axations by acetylcholine are progressively impaired and (3) the endot helium-independent relaxations by nitroprusside are not modified.