Evidence for α-Adrenergic Receptors on Intimal Endothelium

Abstract
The pharmacological effects of norepinephrine covalently bound to large glass beads, applied to the intimal surface of blood vessels, were studied in vitro using rabbit aorta strips. Changes in developed force were recorded using an isometric transducer and a strip chart recorder. A binocular stereomicroscope was used to observe the placement of the small brown-colored beads on the intimal surface. Placement of washed beads in contact with the aortic strip elicited a contraction which peaked within 2 min. It was not maintained as was an equivalent-sized response to l-norepinephrine but slowly relaxed in the continued presence of the beads. Upon removal of the beads the tissue relaxed more rapidly. As few as 5 beads produced a detectable contraction. When the whole intimal surface was lightly covered with beads, a contraction ranging between 52 and 74% of the maximum contraction obtained with high doses of dissolved l-norepinephrine was produced. The response to beads was prevented by pretreating the aorta with the .alpha.-adrenergic receptor blocking agent, phenoxybenzamine (10-5 M). Norepinephrine beads elicited contractions from strips obtained from 8 other types of rabbit arteries and veins. Aortic intima cells were damaged presumably nonspecifically by short-term application of Al2(SO4)3 (10-30 s), which essentially prevented the contractile response to the glass beads, but had less effect on that to dissolved norepinephrine. Either norepinephrine attached to the beads or released norepinephrine in locally high concentration acts on receptors on the intimal surface of the endothelial cells, but the nature of the subsequent change and the mechanism of spread to the subjacent smooth muscle is entirely unknown. Possibly catecholamines and other circulating drugs can initiate changes in the tone of vascular smooth muscle by an action on the intimal endothelial cells. Penetration of the vasoactive drug would not be a necessary prerequisite for changes in vascular diameter.

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