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(Hypertension. 2009;54:29.)
© 2009 American Heart Association, Inc.

Editorial Commentaries

Treatment of Chronic Proteinuric Kidney Disease

What Next?

Ariela Benigni; Giuseppe Remuzzi

From the Mario Negri Institute for Pharmacological Research (A.B., G.R.); and the Division of Nephrology and Dialysis (G.R.), Azienda Ospedaliera Ospedali Riuniti di Bergamo, Bergamo, Italy.

Correspondence to Ariela Benigni, Mario Negri Institute for Pharmacological Research, via Gavazzeni 11, 24125 Bergamo, Italy. E-mail abenigni@marionegri.it

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The vascular endothelium synthesizes and releases a range of vasodilators and vasoconstrictors that have key roles in the local regulation of vascular tone. Among those, endothelin (ET) was identified in 1988 by Yanagisawa et al,¹ as one of the most potent vasoconstrictors known, and so far, the landmark discovery of ET has led to >22 000 publications. These have revealed that ET exerts its activity by binding to 2 types of receptors, namely, ET_A and ET_B, with the ET_A mediating the majority of the deleterious effects of ET in the kidney, including vasoconstriction, cell proliferation, and fibrosis. ET is an important physiological regulator of blood pressure through its effects on blood vessels, heart, and kidneys, and the ET system can be overactive in disorders, eg, hypertension, heart failure, and renal disease.² Such observations have created much interest among researchers and have prompted pharmaceutical companies to set up high-throughput screens to search for antagonists of ET receptors.

The initial observation in 1993 of a renoprotective effect of a selective ET_A receptor antagonist in rats with renal mass reduction³ was further confirmed by a large body of publications that consistently documented the involvement of ET in the process of progressive renal injury in experimental models of nondiabetic and diabetic proteinuric nephropathies.⁴ Animal data also suggested that concomitant blockade of the renin-angiotensin system (RAS) and the ET system displayed more renoprotective effects than blockade of either system alone,⁵ a synergism based on the interaction of angiotensin II (Ang II) and ET at . . . [Full Text of this Article]

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Blood Pressure–Independent Reduction in Proteinuria and Arterial Stiffness After Acute Endothelin-A Receptor Antagonism in Chronic Kidney Disease

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				N. Dhaun, I. M. MacIntyre, V. Melville, P. Lilitkarntakul, N. R. Johnston, J. Goddard, and D. J. Webb Effects of Endothelin Receptor Antagonism Relate to the Degree of Renin-Angiotensin System Blockade in Chronic Proteinuric Kidney Disease Hypertension, September 1, 2009; 54(3): e19 - e20. [Full Text] [PDF]