Barbosa P S F, Martins A M C, Alves R S, Amora D N, Martins R D, Toyama Marcos H, Havt A, Nascimento N R F, Rocha V L C, Menezes D B, Fonteles M C, Monteiro H S A
Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Ceara, Brazil.
Toxicon. 2006 Jun 15;47(8):831-7. doi: 10.1016/j.toxicon.2006.01.012. Epub 2006 May 26.
Renal changes determined by Lys49 myotoxin I (BmTx I), isolated from Bothrops moojeni are well known. The scope of the present study was to investigate the possible mechanisms involved in the production of these effects by using indomethacin (10 microg/mL), a non-selective inhibitor of cyclooxygenase, and tezosentan (10 microg/mL), an endothelin antagonist. By means of the method of mesenteric vascular bed, it has been observed that B. moojeni myotoxin (5 microg/mL) affects neither basal perfusion pressure nor phenylephrine-preconstricted vessels. This fact suggests that the increase in renal perfusion pressure and in renal vascular resistance did not occur by a direct effect on renal vasculature. Isolated kidneys from Wistar rats, weighing 240-280 g, were perfused with Krebs-Henseleit solution. The infusion of BmTx-I increased perfusion pressure, renal vascular resistance, urinary flow and glomerular filtration rate. Sodium, potassium and chloride tubular transport was reduced after addition of BmTx-I. Indomethacin blocked the effects induced by BmTx-I on perfusion pressure and renal vascular resistance, however, it did not revert the effect on urinary flow and sodium, potassium and chloride tubular transport. The alterations of glomerular filtration rate were inhibited only at 90 min of perfusion. The partial blockade exerted by indomethacin treatment showed that prostaglandins could have been important mediators of BmTx-I renal effects, but the participation of other substances cannot be excluded. The blockage of all renal alterations observed after tezosentan treatment support the hypothesis that endothelin is the major substance involved in the renal pathophysiologic alterations promoted by the Lys49 PLA(2) myotoxin I, isolated from B. moojeni. In conclusion, the rather intense renal effects promoted by B. moojeni myotoxin-I were probably caused by the release of renal endothelin, interfering with the renal parameters studied.
从莫氏矛头蝮蛇（Bothrops moojeni）中分离出的Lys49肌毒素I（BmTx I）所引起的肾脏变化是众所周知的。本研究的目的是通过使用吲哚美辛（10微克/毫升）（一种环氧化酶非选择性抑制剂）和替唑生坦（10微克/毫升）（一种内皮素拮抗剂）来研究产生这些效应的可能机制。通过肠系膜血管床方法观察到，莫氏矛头蝮蛇肌毒素（5微克/毫升）既不影响基础灌注压，也不影响去氧肾上腺素预收缩的血管。这一事实表明，肾灌注压和肾血管阻力的增加并非对肾血管系统的直接作用所致。用Krebs-Henseleit溶液灌注体重为240 - 280克的Wistar大鼠的离体肾脏。输注BmTx-I会增加灌注压、肾血管阻力、尿流量和肾小球滤过率。添加BmTx-I后，钠、钾和氯的肾小管转运减少。吲哚美辛可阻断BmTx-I对灌注压和肾血管阻力的诱导作用，然而，它并未逆转对尿流量以及钠、钾和氯肾小管转运的影响。肾小球滤过率的改变仅在灌注90分钟时受到抑制。吲哚美辛治疗所产生的部分阻断作用表明，前列腺素可能是BmTx-I肾脏效应的重要介质，但不能排除其他物质的参与。替唑生坦治疗后观察到的所有肾脏改变均被阻断，这支持了内皮素是由莫氏矛头蝮蛇分离出的Lys49 PLA(2)肌毒素I所引发的肾脏病理生理改变中主要参与物质的假说。总之，莫氏矛头蝮蛇肌毒素-I所引发的相当强烈的肾脏效应可能是由肾内皮素的释放所致，从而干扰了所研究的肾脏参数。
