Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes
- Roland E. Schmieder, MD, FACC1,
- Christian Delles, MD1,
- Albert Mimran, MD2,
- Jean P. Fauvel, MD3 and
- Luis M. Ruilope, MD4
- 1Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany
- 2Department of Medicine, University of Montpellier, Montpellier, France
- 3Department of Nephrology and Arterial Hypertension, Hôpital E. Herriot, Lyon, France
- 4Hypertension Unit, 12 de Octubre Hospital, Madrid, Spain
- Address correspondence and reprint requests to R.E. Schmieder, Clinical Research Center Medizinische Klinik 4, Universitätsklinikum Erlangen, Krankenhausstrasse 12, 91054 Erlangen, Germany. E-mail: roland.schmieder{at}rzmail.uni-erlangen.de
Abstract
OBJECTIVE—One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function.
RESEARCH DESIGN AND METHODS—In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate >80 ml/min, and normo- or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks.
RESULTS—The mean ± SE fall in renal plasma flow (RPF) in response to intravenous NG-monomethyl-l-arginine (l-NMMA), reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 ± 9.0 ml/min before therapy to 105.2 ± 9.7 ml/min at the end of treatment (P < 0.001). With ramipril, RPF response to l-NMMA increased from 60.1 ± 12.2 to 87.8 ± 9.2 ml/min (P = 0.018). The adjusted difference between treatments was −17.1 ± 13.7 ml/min (P = 0.214). In accordance, telmisartan increased RPF at rest (i.e., without l-NMMA) from 652.0 ± 27.0 to 696.1 ± 31.0 ml/min (P = 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r = 0.47, P < 0.001).
CONCLUSIONS—In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function.
- ARB, angiotensin II receptor blocker
- DBP, diastolic blood pressure
- GFR, glomerular filtration rate
- l-NMMA, NG-monomethyl-l-arginine
- MAP, mean arterial pressure
- RAS, renin-angiotensin system
- RPF, renal plasma flow
- SBP, systolic blood pressure
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 2 March 2007. DOI: 10.2337/dc06-1551. Clinical trial reg. no. NCT00240422, clinicaltrials.gov.
R.E.S. has received an honorarium for serving on an advisory board and for and research grants from Boehringer Ingelheim.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted February 19, 2007.
- Received July 27, 2006.
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