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      The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine

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      Nature

      Springer Science and Business Media LLC

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          Abstract

          Despite its very potent vasodilating action in vivo, acetylcholine (ACh) does not always produce relaxation of isolated preparations of blood vessels in vitro. For example, in the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh has been graded contractions, occurring at concentrations above 0.1 muM and mediated by muscarinic receptors. Recently, we observed that in a ring preparation from the rabbit thoracic aorta, ACh produced marked relaxation at concentrations lower than those required to produce contraction (confirming an earlier report by Jelliffe). In investigating this apparent discrepancy, we discovered that the loss of relaxation of ACh in the case of the strip was the result of unintentional rubbing of its intimal surface against foreign surfaces during its preparation. If care was taken to avoid rubbing of the intimal surface during preparation, the tissue, whether ring, transverse strip or helical strip, always exhibited relaxation to ACh, and the possibility was considered that rubbing of the intimal surface had removed endothelial cells. We demonstrate here that relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells, and that ACh, acting on muscarinic receptors of these cells, stimulates release of a substance(s) that causes relaxation of the vascular smooth muscle. We propose that this may be one of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary reports on some aspects of the work have been reported elsewhere.

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          Most cited references 7

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          The importance of phospholipase-A2 in prostaglandin biosynthesis

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            The regeneration of aortic endothelium

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              The Photoactivated Relaxation of Smooth Muscle of Rabbit Aorta

              Smooth muscle of strips of rabbit aorta, placed in a state of active tonic contraction by addition of a stimulating drug, relaxes during exposure to light. The relaxation is reversible. The extent of relaxation produced by a standard exposure depends on the preexposure level of active contraction but not on the nature of the stimulating drug used to produce contraction. With strips brought to an intermediate level of contraction, the degree of relaxation (steady state levels) is a rectangular hyperbolic function of radiation intensity. The kinetics of the relaxation process during irradiation and the recovery process following irradiation are consistent with the hypothesis that the primary photoactivated material initiates a reaction or reactions leading to a product which inhibits some process involved in the production of active contraction. The photorelaxation does not require the presence of oxygen. It is potentiated by reducing the temperature of the aortic strip. The action spectrum of the photorelaxation shows relatively low effectiveness at wavelengths above 450 mµ. The effectiveness increases markedly and progressively as the wavelength is lowered below 450 mµ, reaching a peak at 310 mµ. A deep trough occurs at 280 mµ. However, both peak and trough probably result from internal filtering due to absorption by proteins in the aortic strip. It is surmised that if a correction could be made for this internal filtering, the action spectrum would rise continuously down to wavelengths at least as low as 250 mµ.
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                Author and article information

                Journal
                Nature
                Nature
                Springer Science and Business Media LLC
                0028-0836
                1476-4687
                November 1980
                November 1980
                : 288
                : 5789
                : 373-376
                Article
                10.1038/288373a0
                6253831
                © 1980

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