ALTERED VASOCONSTRICTOR RESPONSIVENESS IN VITAMIN-D-INDUCED ARTERIOSCLEROTIC RAT AORTAS

This investigation was undertaken to characterize the vasoconstrictor responsiveness in aortas isolated from a rat model of arteriosclerosis induced by vitamin D2 (VD) administration followed by feeding with a high-cholesterol diet. Cumulative contractile responses to KCl, noradr enaline and serotonin in thoracic aortic strips isolated from arterios clerotic rats were slightly augmented in concentrations lower than the EC50 value of each agent and rather attenuated in their higher concen trations as compared with those from normal rats. Maximum contractions to the agonists were markedly attenuated in arteriosclerotic aortas; the degree of attenuation was greater in rats treated with a combinati on of VD and cholesterol than in those treated with VD alone. There wa s a significant negative correlation between the maximum contraction t o KCl, noradrenaline or serotonin and the content of calcium or choles terol ester in aortas. Removal of endothelium markedly enhanced sensit ivity and contractility to the agonists in aortic strips from normal r ats, whereas the same procedure only slightly enhanced them in aortic strips from arteriosclerotic rats. These results indicate that in arte riosclerotic rat aortas, contractile responsiveness to agonists of vas cular smooth muscle cells is impaired with deposition of calcium and c holesterol, and they suggest that augmentation of contractile response s to the agonists in lower concentrations is due to impairment of endo thelial function.