Effects of hyperlipidemia on the vascular reactivity in the Wistar-Kyoto and spontaneously hypertensive rats

Abstract

We studied the effects of hyperlipidemia on the vascular responsiveness in aortas isolated from control rats and rats receiving a high cholesterol-high fat (HC-HF) diet (1% cholesterol and 20% olive oil). The total plasma cholesterol, very low density lipoprotein (VLDL)-, low density lipoprotein (LDL)-cholesterol, VLDL-, LDL-, high density lipoprotein (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 plasma cholesterol and triglyceride levels were time-dependent. Higher levels of cholesterol and triglyceride were observed in SHR compared to WKY. 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 aortic arches of SHR and WKY were significantly more affected by the intimal lesion (surface area damage and fatty streak formation) than the abdominal 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 phenylephrine (0.01–30 μM)-induced contraction were obtained. Endothelium-dependent relaxation to acetylcholine was abolished, while endothelium-independent relaxation to nitroprusside was well preserved in the denuded aortic arches and abdominal aortas of the WKY, SHR rats with or without 8 week HC-HF diet. We conclude from these studies that in the isolated aortas from hyperlipidemic WKY and SHR: (1) the contractions induced by phenylephrine are augmented, (2) the endothelium-dependent relaxations by acetylcholine are progressively impaired and (3) the endothelium-independent relaxations by nitroprusside are not modified.