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

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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. In the helical strip of the rabbit descending thoracic aorta, the only reported response to ACh was graded contractions, occurring at concentrations > 0.1 .mu.M and mediated by muscarinic receptors. 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, it was discovered that the loss of relaxation by ACh in the case of the strip was due to 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; the possibility was considered that rubbing of the intimal surface had removed endothelial cells. Relaxation of isolated preparations of rabbit thoracic aorta and other blood vessels by ACh requires the presence of endothelial cells and ACh, acting on muscarinic receptors of these cells, to stimulate release of a substance(s) that causes relaxation of the vascular smooth muscle. This may be 1 of the principal mechanisms for ACh-induced vasodilation in vivo. Preliminary resports on some aspects of the work were reported.