(Hypertension. 2001;37:1108.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Vasopeptidase Inhibition Exhibits Endothelial Protection in Salt-Induced Hypertension
From Cardiovascular Research, Institute of Physiology, University of Zürich, (T.Q., L.V.d’U.); Cardiology, University Hospital Zürich (T.F.L); and Clinical Research, University of Bern (S.S.), Switzerland.
Correspondence to Thomas F. Lüscher, MD, FRCP, FACC, University Hospital, Department of Cardiology, Rämistr 100, CH-8091 Zürich, Switzerland. E-mail cardiotfl{at}compuserve.com
Abstract—Omapatrilat represents a new class of drugs capable of inhibiting both ACE and neutral endopeptidase 24.11, the so-called vasopeptidase inhibitors. It therefore contributes to neurohumoral modulation, which might improve endothelial function in cardiovascular diseases. This study investigated the effect of omapatrilat in comparison to the ACE inhibitor captopril on systolic blood pressure and endothelial function in salt-induced hypertension. Dahl salt-sensitive rats (n=6/group) on standard or salt-enriched (4% NaCl) chow were treated for 8 weeks with either omapatrilat (36±4 mg/kg per day), captopril (94±2 mg/kg per day), or placebo. Aortic rings were then isolated and suspended in organ chambers for isometric tension recording. Systolic blood pressure of salt-fed, placebo-treated animals increased to 196±6 mm Hg, which was prevented by omapatrilat (162±5 mm Hg, P<0.05) and captopril (164±7 mm Hg, P<0.05) to a comparable degree. In control rats, acetylcholine (10-10 to 10-5 mol/L) induced endothelium-dependent relaxation (97±4%), which was reduced by high-salt diet to 30±5% (P<0.005; n=6). Omapatrilat improved relaxation to a greater extent (86±5%) than did captopril (57±6%; P<0.05). eNOS protein expression and aortic nitrite/nitrate content were reduced in hypertensive rats and improved by both omapatrilat and captopril. Aortic endothelin-1 levels were increased in salt-fed animals and unaffected by omapatrilat or captopril. These data suggest that despite comparable blood pressure, omapatrilat is superior to captopril in improving endothelium-dependent relaxation in salt-sensitive hypertension.
Key Words: hypertension, sodium-dependent • endothelium • captopril • nitric oxide
This article has been cited by other articles:
 |
|
 |
|
  A. J. Flammer, I. Sudano, F. Hermann, S. Gay, A. Forster, M. Neidhart, P. Kunzler, F. Enseleit, D. Periat, M. Hermann, et al. Angiotensin-Converting Enzyme Inhibition Improves Vascular Function in Rheumatoid Arthritis Circulation, April 29, 2008; 117(17): 2262 - 2269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Quaschning, F. Voss, K. Relle, P. Kalk, N. Vignon-Zellweger, T. Pfab, C. Bauer, F. Theilig, S. Bachmann, A. Kraemer-Guth, et al. Lack of Endothelial Nitric Oxide Synthase Promotes Endothelin-Induced Hypertension: Lessons from Endothelin-1 Transgenic/Endothelial Nitric Oxide Synthase Knockout Mice J. Am. Soc. Nephrol., March 1, 2007; 18(3): 730 - 740. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pfister, N. E. Martin, L. P. Haskell, and J. S. Barrett Optimizing Dose Selection with Modeling and Simulation: Application to the Vasopeptidase Inhibitor M100240 J. Clin. Pharmacol., June 1, 2004; 44(6): 621 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhu, T. Mori, T. Huang, and J. H. Lombard Effect of high-salt diet on NO release and superoxide production in rat aorta Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H575 - H583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Ebihara, G. Seno Di Marco, M. Aparecida Juliano, and D. E. Casarini Neutral endopeptidase expression in mesangial cells Journal of Renin-Angiotensin-Aldosterone System, December 1, 2003; 4(4): 228 - 233. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Schuh, T. Quaschning, S. Knauer, K. Hu, S. Kocak, N. Roethlein, and L. Neyses Regulation of Vascular Tone in Animals Overexpressing the Sarcolemmal Calcium Pump J. Biol. Chem., October 17, 2003; 278(42): 41246 - 41252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. O. Wenzel, G. Wolf, I. Jacob, C. Schwegler, A. Qasqas, K. Amann, U. Helmchen, and R. A. K. Stahl Beneficial and adverse renal and vascular effects of the vasopeptidase inhibitor omapatrilat in renovascular hypertensive rats Nephrol. Dial. Transplant., October 1, 2003; 18(10): 2005 - 2013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Quaschning, S. Kocak, C. Bauer, H.-H. Neumayer, J. Galle, and B. Hocher Increase in nitric oxide bioavailability improves endothelial function in endothelin-1 transgenic mice Nephrol. Dial. Transplant., March 1, 2003; 18(3): 479 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. V. Maniu, D. M. Meyer, and M. M. Redfield Hemodynamic and Humoral Effects of Vasopeptidase Inhibition in Canine Hypertension Hypertension, October 1, 2002; 40(4): 528 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Mitchell, J. L. Izzo Jr, Y. Lacourciere, J.-P. Ouellet, J. Neutel, C. Qian, L. J. Kerwin, A. J. Block, and M. A. Pfeffer Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients With Systolic Hypertension: Results of the Conduit Hemodynamics of Omapatrilat International Research Study Circulation, June 25, 2002; 105(25): 2955 - 2961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Corti, J. C. Burnett Jr, J. L. Rouleau, F. Ruschitzka, and T. F. Luscher Vasopeptidase Inhibitors: A New Therapeutic Concept in Cardiovascular Disease? Circulation, October 9, 2001; 104(15): 1856 - 1862. [Abstract] [Full Text] [PDF]
|
|