Longaretti L, Benigni A
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Eur J Clin Invest. 2009 Jun;39 Suppl 2:32-7. doi: 10.1111/j.1365-2362.2009.02119.x.
Chronic kidney diseases are increasing worldwide at an alarming rate, and they are emerging as a major public health problem. Treatments that slow the progression of chronic kidney disease are needed. Endothelin-1 (ET-1) is a potent vasoconstrictor with proinflammatory, mitogenic and profibrotic effects that is closely involved in both normal renal physiology and pathology. Increasing evidence suggests that ET-1 and its cognate receptors are involved in a variety of progressive renal disorders to the extent that renal ET-1 expression correlates with disease severity and renal function impairment. Endothelin receptor antagonists have been used in renoprotection studies owing to their capacity of improving renal hemodynamics and reducing proteinuria. Whether selective ET(A) or non-selective ET(A)/ET(B) receptor antagonists are preferable is still a matter of debate. As angiotensin II blockers are not invariably effective in retarding disease progression when treatment is started late in the course of the disease, it is foreseeable that an ET-1 antagonist in addition to angiotensin-converting enzyme inhibitors could represent a combined treatment for progressive nephropathies. The focus of this review is to examine the role endothelin-1 plays in kidney diseases and to determine the ideal setting for antagonizing its biological activity in chronic nephropathies.
慢性肾脏病在全球范围内正以惊人的速度增长，并且正成为一个主要的公共卫生问题。需要有能够减缓慢性肾脏病进展的治疗方法。内皮素-1（ET-1）是一种强效血管收缩剂，具有促炎、促有丝分裂和促纤维化作用，它与正常肾脏生理及病理过程都密切相关。越来越多的证据表明，ET-1及其同源受体在多种进行性肾脏疾病中发挥作用，以至于肾脏ET-1表达与疾病严重程度及肾功能损害相关。内皮素受体拮抗剂因其改善肾脏血流动力学和减少蛋白尿的能力，已被用于肾脏保护研究。选择性ET(A)受体拮抗剂还是非选择性ET(A)/ET(B)受体拮抗剂更具优势仍存在争议。由于当在疾病病程后期开始治疗时，血管紧张素II阻滞剂在延缓疾病进展方面并非总是有效，因此可以预见，除血管紧张素转换酶抑制剂外，ET-1拮抗剂可能是一种针对进行性肾病的联合治疗方法。本综述的重点是研究内皮素-1在肾脏疾病中的作用，并确定在慢性肾病中拮抗其生物活性的理想时机。
