Vasopeptidase inhibition normalizes blood pressure and restores endothelial function in renovascular hypertension
| Autor: | Johannes Tilgner, Christoph Wanner, Sabine Rühl, Jan Galle, Berthold Hocher, Annette Kraemer-Guth, Thomas Quaschning |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Hypertension Renal Endothelium Angiotensin-Converting Enzyme Inhibitors Blood Pressure Pharmacology Peptidyl-Dipeptidase A Rats Inbred WKY Renovascular hypertension Nitric oxide chemistry.chemical_compound Ramipril Heart Rate medicine Vasopeptidase Inhibitors Animals Neprilysin Endothelin-1 business.industry fungi General Medicine medicine.disease Rats Vasodilation medicine.anatomical_structure Blood pressure chemistry Nephrology ACE inhibitor Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine business Heterocyclic Compounds 3-Ring Vasoconstriction medicine.drug |
| Zdroj: | Kidneyblood pressure research. 29(6) |
| ISSN: | 1420-4096 |
| Popis: | Background/Aims: Vasopeptidase inhibitors by definition inhibit both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), therefore they may exceed the effect of ACE inhibitors in the treatment of hypertension. The present study investigated the effect of the vasopeptidase inhibitor AVE7688 in comparison to the ACE inhibitor ramipril on systolic blood pressure (SBP) and endothelial function in renovascular hypertension. Methods: Wistar-Kyoto rats with renovascular hypertension (two-kidney one-clamp-model) were randomized 2 weeks after unilateral clamping of the right renal artery for 3 weeks’ oral treatment with either AVE7688 (30 mg/kg/day), ramipril (1 mg/kg/day) or placebo. SBP was measured by the tail-cuff method and endothelium-dependent and -independent vascular function was assessed in isolated preconstricted (norepinephrine 10–7 mol/l) aortic rings as relaxation to acetylcholine (10–10–10–4 mol/l) and sodium nitroprusside (10–10–10–4 mol/l), respectively. Results: Two weeks after clamping, SBP was significantly elevated (196 ± 16 vs. 145 ± 8 mm Hg for sham-operated rats; p < 0.01) and further increased in placebo-treated animals to 208 ± 19 mm Hg. Treatment with AVE7688 and ramipril had a similar blood pressure-lowering effect (119 ± 8 and 124 ± 10 mm Hg, respectively; p < 0.01 vs. placebo). Maximum endothelium-dependent relaxation was reduced in hypertensive rats (72 ± 6 vs. 99 ± 7% in control rats; p < 0.05). Endothelium-dependent relaxation was restored by AVE7688 (101 ± 6%) and ramipril (94 ± 8%), respectively, whereas endothelium-independent relaxation was comparable in all groups. Conclusion: In renovascular hypertension the vasopeptidase inhibitor AVE7688 exhibited similar blood pressure-lowering and endothelial protective properties as compared to the ACE inhibitor ramipril. Therefore, in high renin models of hypertension, vasopeptidase inhibition may be considered an alternative treatment option to ACE inhibition. |
| Databáze: | OpenAIRE |
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