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

我们研究了apelin和APJ转录本的存在，发现在肺、心、脑、卵巢、肠和血细胞中都有高水平的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表达于脂肪细胞和动脉平滑肌细胞。大鼠静脉注射apelin-12、apelin-13和apelin-36可显著降低动脉血压，但对心率无影响。在降低这些大鼠的平均动脉压(MAP)方面，apelin-12比apelin-13或apelin-36更有效。相反，apelin-9、apelin-10和apelin-11对MAP没有影响，提示apelin-36的C-末端至少有12个氨基酸残基是其生物学活性所必需的。我们还观察了一氧化氮合酶抑制剂-N^G-硝基-L-精氨酸甲酯(L-NAME)对APELIN-12降压反应的影响。对照组大鼠注射apelin-12后，注射apelin-12可引起MAP下降。而给予相同剂量的APELIN-12，对L-NAME组大鼠的MAP几乎没有影响，表明在L-NAME存在下，APELIN-12的作用几乎完全消失。我们还发现，apelin显著增加了大鼠血浆中NOx的浓度。这些结果提示，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.