Tension-Induced Release of Endothelium-Derived Relaxing Factor; Possible Role in Establishment of Desensitization of Norepinephrine-Induced Contraction in Rat Aorta

In order to clarify the mechanisms involved in the endothelium-dependent development of desensitization of norepinephrine-induced contraction in rat aorta, we have tested the effect of repeated generation of tension without receptor stimulation. Even when tension alone, with a magnitude almost equal to that generated by norepinephrine, was applied to the endothelium-intact ring without norepinephrine, the ring became desensitized. In the absence of endothelium, the development of desensitization did not occur. Furthermore, L-NG-monomethyl arginine, which is an inhibitor of endothelium-dependent relaxing factor (EDRF) synthesis, prevented the occurrence of desensitization. It was even able to reestablish contractile force when added after the desensitization had developed, suggesting that an increased release of EDRF is necessary to produce the desensitization. Therefore, these results indicate that endothelium-dependent desensitization does not require adrenergic receptor stimulation, but rather that tension generation alone is sufficient to establish desensitization.