ALTERED CATECHOLAMINE RECEPTOR AFFINITY IN RABBIT AORTIC INTIMAL HYPERPLASIA

Intimal thickening is a universal response to endothelial denudation and is also thought to be a precursor of atherosclerosis. We have demonstrated selective supersensitivity in arterial intimal hyperplasia to norepinephrine and we now report a possible mechanism for this. Binding studies in rabbit aorta with the selective α1-adrenergic radioligand 125I-HEAT demonstrated that there was no change in receptor density (20 ± 4 fmole/106 cells) in intact vascular smooth muscle cells at either 5 or 14 days after denudation. However, competition studies showed a 2.6-fold increase in α1-adrenergic receptor affinity for norepinephrine in intimal hyperplastic tissue (P < 0.05). This increased affinity for norepinephrine was associated with a greater increase in 32P-labeled phosphatidylinositol (148% intimal thickening versus 76% control) and phosphatidic acid (151% intimal thickening versus 56% control) following norepinephrine stimulation of free floating rings of intimal hyperplastic aorta. These data suggest that the catecholamine supersensitivity in rabbit aortic intimal hyperplasia is receptor mediated and may be linked to the phosphatidylinositol cycle. © 1991.