The article by Robert F. Furchgott discusses the role of endothelial cells in the relaxation of vascular smooth muscle. Key findings include: 1. **Endothelial Cell Requirement**: Acetylcholine (ACh) induces relaxation in isolated arteries only when endothelial cells are present. This requirement is observed in various mammalian species and arteries, including rabbit, dog, cat, and human. 2. **Mechanism of Relaxation**: ACh relaxes arteries by stimulating muscarinic receptors on endothelial cells, which then release a factor (EDRF) that acts on the smooth muscle cells to cause relaxation. 3. **Inhibition of Relaxation**: Agents like anoxia, etepronol, quinacrine, nordihydroguaiaretic acid (NDGA), hydroquinone, and p-bromophenacyl bromide (BPB) can inhibit ACh-induced relaxation. These agents interfere with different aspects of the relaxation process, such as calcium ion influx or phospholipase A2 activity. 4. **Calcium's Role**: Calcium ions are crucial for the release of EDRF. The calcium ionophore A23187, which increases calcium influx, also requires endothelial cells for its relaxing effect and is more potent than ACh. 5. **Other Relaxing Agents**: ATP, ADP, bradykinin, substance P, histamine, thrombin, and arachidonic acid (AA) also produce endothelium-dependent relaxations. These agents often require endothelial cells for their relaxing effects and are influenced by similar inhibitors as ACh. 6. **Prostaglandins**: Prostaglandins, particularly prostacyclin (PGI2), are not involved in the endothelium-dependent relaxation by ACh or bradykinin. However, bradykinin can stimulate the release of prostaglandins in some arteries. 7. **Endothelial Cell Loss**: In some experiments, complete loss of endothelial cells from the intimal surface results in the loss of ACh-induced relaxation, suggesting that endothelial cells are essential for this process. 8. **Sensitivity to Relaxation**: The sensitivity of arteries to ACh and other relaxing agents varies, with some arteries being more sensitive than others. For example, rabbit aorta is more sensitive to ACh than canine femoral artery. 9. **Direct and Indirect Actions**: ATP and ADP relax arteries by both direct action on muscle cells and indirect action via endothelial cells. AMP and adenosine relax arteries directly, but their endothelium-dependent relaxation is not inhibited by cyclooxygenase inhibitors. 10. **Conclusion**: The endothelium plays a critical role in the relaxation of vascular smooth muscle, and the release of EDRF from endothelial cells is a key mechanism. This process is influenced by various factors, including calcium levels and the presence of specific agents.The article by Robert F. Furchgott discusses the role of endothelial cells in the relaxation of vascular smooth muscle. Key findings include: 1. **Endothelial Cell Requirement**: Acetylcholine (ACh) induces relaxation in isolated arteries only when endothelial cells are present. This requirement is observed in various mammalian species and arteries, including rabbit, dog, cat, and human. 2. **Mechanism of Relaxation**: ACh relaxes arteries by stimulating muscarinic receptors on endothelial cells, which then release a factor (EDRF) that acts on the smooth muscle cells to cause relaxation. 3. **Inhibition of Relaxation**: Agents like anoxia, etepronol, quinacrine, nordihydroguaiaretic acid (NDGA), hydroquinone, and p-bromophenacyl bromide (BPB) can inhibit ACh-induced relaxation. These agents interfere with different aspects of the relaxation process, such as calcium ion influx or phospholipase A2 activity. 4. **Calcium's Role**: Calcium ions are crucial for the release of EDRF. The calcium ionophore A23187, which increases calcium influx, also requires endothelial cells for its relaxing effect and is more potent than ACh. 5. **Other Relaxing Agents**: ATP, ADP, bradykinin, substance P, histamine, thrombin, and arachidonic acid (AA) also produce endothelium-dependent relaxations. These agents often require endothelial cells for their relaxing effects and are influenced by similar inhibitors as ACh. 6. **Prostaglandins**: Prostaglandins, particularly prostacyclin (PGI2), are not involved in the endothelium-dependent relaxation by ACh or bradykinin. However, bradykinin can stimulate the release of prostaglandins in some arteries. 7. **Endothelial Cell Loss**: In some experiments, complete loss of endothelial cells from the intimal surface results in the loss of ACh-induced relaxation, suggesting that endothelial cells are essential for this process. 8. **Sensitivity to Relaxation**: The sensitivity of arteries to ACh and other relaxing agents varies, with some arteries being more sensitive than others. For example, rabbit aorta is more sensitive to ACh than canine femoral artery. 9. **Direct and Indirect Actions**: ATP and ADP relax arteries by both direct action on muscle cells and indirect action via endothelial cells. AMP and adenosine relax arteries directly, but their endothelium-dependent relaxation is not inhibited by cyclooxygenase inhibitors. 10. **Conclusion**: The endothelium plays a critical role in the relaxation of vascular smooth muscle, and the release of EDRF from endothelial cells is a key mechanism. This process is influenced by various factors, including calcium levels and the presence of specific agents.