[Hyperlipidemia impairs vascular endothelium-dependent relaxation in pig coronary arteries]

We examined the effects of a low pathophysiological level of hyperlipidemia and atherogenic lipoprotein (LDL) on the vascular responsiveness of isolated pig coronary arteries. Firstly, we studied the change of vascular responsiveness after feeding a cholesterol-rich diet to pigs for 4 or 9 weeks. Serum cholesterol level in pigs fed with the cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in controls. Segments of the arteries were mounted in organ chambers for isometric tension recording. Contraction caused by KCl or prostaglandin F2 alpha was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered significantly by hypercholesterolemia. Relaxation in response to Ca2+ ionophore A23187 or nitroglycerin was not altered. Endothelium-dependent relaxation evoked by high but not low concentrations of bradykinin and substance P were reduced in pigs fed with the cholesterol-rich diet for 4 weeks as compared with those in normal pigs. Those evoked by bradykinin, substance P, and serotonin were significantly reduced in pigs fed with the cholesterol-rich diet for 9 weeks. Histologically, the fatty changes or intimal thickening were not so evident in coronary arteries of pigs fed for 4 weeks with the cholesterol-rich diet, but only minimal changes were observed in those fed with the diet for 9 weeks by light or electron microscopy. Secondly, the direct effects of LDL on the vascular responsiveness were examined.(ABSTRACT TRUNCATED AT 250 WORDS)