Pharmacological studies on a novel biologically active peptide apelin produced in the adipocytes

我们研究了apelin和APJ转录物的存在，发现肺、心脏、脑、卵巢、肠和血细胞中有高水平的apelin mRNA。它也存在于脂肪细胞、动脉内皮细胞、胃粘膜细胞和T细胞中。Apelin受体APJ mRNA见于脂肪细胞和动脉平滑肌细胞。发现在大鼠中静脉内施用爱帕琳-12、爱帕琳-13和爱帕琳-36显著降低动脉血压，而心率没有变化。爱帕琳-12在降低这些大鼠的平均动脉压（MAP）方面比爱帕琳-13或爱帕琳-36更有效。相比之下，爱帕琳-9、爱帕琳-10和爱帕琳-11对MAP没有影响，这表明具有至少12个氨基酸残基的爱帕琳-36的C末端部分可能是其生物活性所需的。我们还研究了一氧化氮合成抑制剂N^G-硝基-L-精氨酸甲酯（L-NAME）对大鼠apelin-12降压反应的影响。在对照大鼠中，爱帕琳-12注射后，爱帕琳-12的施用诱导MAP降低。然而，在用L-NAME预处理的大鼠中，给予相同剂量的apelin-12几乎没有引起MAP的变化，这表明在L-NAME存在下apelin-12的作用几乎完全消除。我们还发现，apelin显着增加大鼠血浆NOx浓度。这些结果表明，apelin的降压反应可能依赖于一氧化氮的释放。

We investigated the presence of apelin and APJ transcripts and found high levels of apelin mRNA in the lung, heart, brain, ovary, intestine, and blood cells. It also presents in the adipocytes, arterial endothelial cells, gastric mucosal cells, and T cells. Apelin receptor APJ mRNA is seen in the adipocytes and arterial smooth muscle cells. The intravenous administration of apelin-12, apelin-13, and apelin-36 in the rats was found to significantly lower arterial blood pressure with no change in heart rate. Apelin-12 was more potent than apelin-13 or apelin-36 in reducing mean arterial pressure (MAP) in these rats. In contrast, apelin-9, apelin-10, and apelin-11 had no effect on MAP, suggesting that the C-terminal portion of apelin-36 with at least 12 amino acid residues may be required for its biological activity. We also examined the effects of a nitric oxide synthesis inhibitor, N^G-nitro-L-arginine methyl ester (L-NAME), on the depressor response of apelin-12 in the rats. The administration of apelin-12 induced the decrease in MAP after apelin-12 injection in the control rats. However, the administration of the same dose of apelin-12 caused almost no change in MAP in the rats pretreated with L-NAME, indicating that the action of apelin-12 was almost completely abolished in the presence of L-NAME. We also found that apelin significantly increased plasma NOx concentrations in rats. These results suggest that the depressor response of apelin may be dependent upon the release of nitric oxide.