Morrissey J J, Klahr S
Department of Internal Medicine, Washington University School of Medicine, Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
Proc Assoc Am Physicians. 1997 Jan;109(1):51-7.
Agmatine is a product of arginine decarboxylation. Systemic infusion of agmatine into rats causes hypotension. This effect could be due either to a central action of agmatine (a clonidine displacing substance), or to a direct effect of agmatine on cells of blood vessel walls, which induces them to cause vasodilatation, or both. In this study, we examined the effects of agmatine on endothelial cell function by using cultured bovine pulmonary artery endothelial cells. Agmatine stimulated nitrite production three-fold above basal nitrite formation by endothelial cells. The increased nitrite production by agmatine was inhibited by idazoxan but not by yohimbine. Agmatine displaced [3H]-idazoxan from endothelial cell membranes and was found to induce transients in the cytosolic calcium of endothelial cells. The transients could be downregulated by repeated exposure to agmatine but were not affected by pretreatment with norepinephrine. These results suggest that agmatine can bind to a cell surface imidazoline receptor on endothelial cells and can stimulate nitric oxide production by increasing cytosolic calcium. Therefore, agmatine appears to act directly on endothelial cells to increase the synthesis of nitric oxide, a vasodilatory substance.
胍丁胺是精氨酸脱羧的产物。向大鼠体内全身输注胍丁胺会导致低血压。这种效应可能是由于胍丁胺的中枢作用（一种可乐定置换物质），或者是胍丁胺对血管壁细胞的直接作用，促使血管壁细胞引起血管舒张，或者两者皆有。在本研究中，我们通过使用培养的牛肺动脉内皮细胞来研究胍丁胺对内皮细胞功能的影响。胍丁胺刺激内皮细胞产生的亚硝酸盐比基础亚硝酸盐生成量高出三倍。胍丁胺导致的亚硝酸盐生成增加被咪唑克生抑制，但未被育亨宾抑制。胍丁胺从内皮细胞膜上置换出[³H] - 咪唑克生，并被发现可诱导内皮细胞胞质钙的瞬变。通过反复暴露于胍丁胺，这些瞬变可以被下调，但不受去甲肾上腺素预处理的影响。这些结果表明，胍丁胺可以与内皮细胞表面的咪唑啉受体结合，并通过增加胞质钙来刺激一氧化氮的产生。因此，胍丁胺似乎直接作用于内皮细胞以增加血管舒张物质一氧化氮的合成。
