The role of endothelium-derived nitric oxide (NO) in regulating blood pressure was investigated using L-NMMA, a specific inhibitor of NO synthesis from L-arginine. In anesthetized rabbits, L-NMMA (3–100 mg·kg⁻¹) caused a dose-dependent increase in mean arterial blood pressure, while its D-enantiomer did not. L-NMMA also inhibited the hypotensive effect of acetylcholine (ACh) but not that of glyceryl trinitrate. These effects were reversed by L-arginine but not by D-arginine or other drugs. L-NMMA inhibited NO release from perfused aortic segments, which was reversed by L-arginine. These results suggest that NO from the vascular endothelium plays a role in blood pressure regulation and in the hypotensive actions of ACh. Endothelium-dependent vascular relaxation and the release of endothelium-derived relaxing factor (EDRF) have been established in vitro, but their in vivo occurrence is only circumstantial. Changes in vessel diameter following blood flow changes are endothelium-dependent. Damage to the endothelium or treatment with nonspecific inhibitors of endothelium-dependent relaxation abolish responses to endothelium-dependent vasodilators without affecting those to endothelium-independent ones. NO is the biological mediator of EDRF and is formed by vascular endothelial cells from L-arginine. L-NMMA inhibits NO synthesis and endothelium-dependent relaxation, indicating that L-arginine is the physiological precursor for NO synthesis by the vascular endothelium. The study used L-NMMA to investigate the role of NO in blood pressure regulation in anesthetized rabbits. In vivo, L-NMMA caused dose-dependent hypertension, which was reversed by L-arginine. ACh and n₃Gro caused dose-dependent hypotension, which was enhanced by L-NMMA. L-NMMA inhibited ACh-induced hypotension but not that of n₃Gro. L-arginine restored NO release in aortae from L-NMMA-treated animals. These findings suggest that NO formation contributes to blood pressure regulation. The study indicates that the vascular endothelium, by synthesizing NO from L-arginine, plays a significant role in blood pressure control. The results suggest that NO synthesis is involved in the regulation of blood pressure and that changes in NO synthesis or action may contribute to hypertension. Further research is needed to determine the long-term effects of altering vascular reactivity and inducing experimental hypertension.The role of endothelium-derived nitric oxide (NO) in regulating blood pressure was investigated using L-NMMA, a specific inhibitor of NO synthesis from L-arginine. In anesthetized rabbits, L-NMMA (3–100 mg·kg⁻¹) caused a dose-dependent increase in mean arterial blood pressure, while its D-enantiomer did not. L-NMMA also inhibited the hypotensive effect of acetylcholine (ACh) but not that of glyceryl trinitrate. These effects were reversed by L-arginine but not by D-arginine or other drugs. L-NMMA inhibited NO release from perfused aortic segments, which was reversed by L-arginine. These results suggest that NO from the vascular endothelium plays a role in blood pressure regulation and in the hypotensive actions of ACh. Endothelium-dependent vascular relaxation and the release of endothelium-derived relaxing factor (EDRF) have been established in vitro, but their in vivo occurrence is only circumstantial. Changes in vessel diameter following blood flow changes are endothelium-dependent. Damage to the endothelium or treatment with nonspecific inhibitors of endothelium-dependent relaxation abolish responses to endothelium-dependent vasodilators without affecting those to endothelium-independent ones. NO is the biological mediator of EDRF and is formed by vascular endothelial cells from L-arginine. L-NMMA inhibits NO synthesis and endothelium-dependent relaxation, indicating that L-arginine is the physiological precursor for NO synthesis by the vascular endothelium. The study used L-NMMA to investigate the role of NO in blood pressure regulation in anesthetized rabbits. In vivo, L-NMMA caused dose-dependent hypertension, which was reversed by L-arginine. ACh and n₃Gro caused dose-dependent hypotension, which was enhanced by L-NMMA. L-NMMA inhibited ACh-induced hypotension but not that of n₃Gro. L-arginine restored NO release in aortae from L-NMMA-treated animals. These findings suggest that NO formation contributes to blood pressure regulation. The study indicates that the vascular endothelium, by synthesizing NO from L-arginine, plays a significant role in blood pressure control. The results suggest that NO synthesis is involved in the regulation of blood pressure and that changes in NO synthesis or action may contribute to hypertension. Further research is needed to determine the long-term effects of altering vascular reactivity and inducing experimental hypertension.