Pharmacological vascular reactivity in isolated hypercholesterolemic rabbit ciliary artery

We have investigated functional and morphological changes occurring in the wall of the hypercholesterolemic rabbit ciliary artery. A mutant rabbit with hypercholesterolemia and atherosclerosis was created by serial breeding. Ciliary arteries from hypercholesterolemic, age-matched control and young control rabbits' eyes were mounted in a myograph system. The effects of phenylephrine (PE), carbachol and electrical field stimulation on this artery were investigated using isometric tension recording methods. The arteries were also examined morphologically. PE caused dose-dependent contraction in young control, age-matched control and hypercholesterolemic rabbits. The EC(50) values were 1.0 microm (0.2-2.1, n = 6), 1.4 microm (0.4-2.4, n = 6) and 4.7 microm (1.8-7.7, n = 8) in the young, age-matched controls and in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits, respectively. The EC(50) values of the KHC rabbit were significantly different from those of control. Electrical field stimulation evoked contraction only in the control rabbits. On the other hand, electrical field stimulation evoked relaxation when the ciliary artery was pre-contracted by 10 microm histamine in each type of rabbit equally. Carbachol also induced approximately equal dose-dependent relaxation after pre-contraction. The morphological findings of KHC rabbit ciliary artery revealed irregular contours on the internal elastic lamina and deformation of the shape of the medial smooth muscle cells with irregularity in size and widening of the intercellular spaces. However, the endothelial cells were well preserved. Compared with the ciliary artery, typical atherosclerotic changes existed in the intima, not the media, in the KHC rabbit aorta. In the hypercholesterolemic rabbit ciliary artery, the vasoconstricting function was reduced but vasodilatation was well preserved. Morphological findings supported this. The pharmacological vascular reactivity in the hypercholesterolemic rabbit ciliary artery is quite different from that of the large arteries.