Published online before print May 19, 2008, doi: 10.1161/HYPERTENSIONAHA.108.113480
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(Hypertension. 2008;52:63.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
Antihypertensive and Renoprotective Mechanisms of Renin Inhibition in Diabetic Rats
From the Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville.
Correspondence to Dr Robert M. Carey, P.O. Box 801414, University of Virginia Health System, Charlottesville, VA 22908-1414. E-mail rmc4c@virginia.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Diabetic nephropathy, the most common cause of end-stage renal disease (ESRD) in the Western world, is characterized by suppression of the systemic but activation of the intrarenal tissue renin-angiotensin system (RAS).1 Blockade of the RAS with angiotensin converting enzyme (ACE) inhibitors or angiotensin type-1 receptor blockers (ARBs) retards but does not eliminate the progression of diabetic nephropathy to ESRD in prospective, randomized, controlled clinical trials.2–4 Studies have demonstrated that a major component of tissue protection from RAS blockers derives from reduction in blood pressure.5 However, a possibility for failure to prevent completely the decline in renal function attributable to tissue damage is that the activity of the intrarenal RAS may be inadequately suppressed by these drugs.
Renin, an aspartyl protease cleaving angiotensinogen (Agt) at the origin of the angiotensin peptide cascade, has been a logical target for RAS inhibition. Since 1982, when the first peptide analogues of Agt were designed to block its catalytic cleavage by renin,6 multiple attempts have been made to inhibit renin, first by dipeptide transition-state analogue inhibitors of the renin active site and most recently by nonpeptide compounds, of which aliskiren is the most successful example.7 Aliskiren, approved for the treatment of hypertension in 2007, decreases plasma renin activity, angiotensin I and angiotensin II concentrations, and blood pressure in hypertensive patients.7 The blood pressure reduction of aliskiren is additive to that of ACE inhibitors, ARBs, and diuretics by preventing the increase in plasma renin activity accompanying the use of these agents.7 In spite of its inhibition
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