Document Detail


Chronic treatment with long-acting nifedipine reduces vasoconstriction to endothelin-1 in essential hypertension.
MedLine Citation:
PMID:  17178974     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Essential hypertension is associated with enhanced biological activity of endothelin-1 (ET-1) and impaired endothelium-dependent vasodilatation. Dihydropyridine calcium antagonists have antioxidant activity in vitro, and they improve endothelial function in vivo. We tested whether calcium antagonists also influence the biological activity of ET-1 in essential hypertensive (EH) patients in the presence and absence of hypercholesterolemia. In 9 healthy subjects (normotensive [NT] subjects, age: 48.3+/-7.6 years; blood pressure: 118+/-8.6/69+/-5.4 mm Hg) and 21 EH subjects (age: 50.0+/-7.8 years; blood pressure: 164.4+/-5.4/103.8+/-4.4 mm Hg), we studied forearm blood flow and its modification induced by intrabrachial administration of ET-1, phenylephrine, acetylcholine, and sodium nitroprusside at baseline and after 24 weeks of treatment with a nifedipine gastrointestinal therapeutic system (30 to 60 mg per day). At baseline, the first dose of ET-1 (0.5 microg/100 mL of forearm tissue per minute) caused a slight vasodilatation in NT but not in EH subjects, whereas the following higher doses caused a comparable dose-dependent vasoconstriction in EH and NT subjects. The effect of acetylcholine was significantly reduced in EH as compared with NT subjects. In contrast, sodium nitroprusside and phenylephrine had similar effects in NT and EH subjects. After chronic treatment with the nifedipine gastrointestinal therapeutic system, the vasoconstrictor effect induced by both ET-1 and phenylephrine was significantly blunted, whereas the response to acetylcholine was significantly increased and the vasodilation to sodium nitroprusside unchanged. Hypercholesterolemic EH subjects showed a further reduced response to acetylcholine compared with normocholesterolemic EH subjects, and the nifedipine gastrointestinal therapeutic system restored the vasodilation to acetylcholine in this subgroup. In conclusion, in EH subjects, chronic treatment with a long-acting dihydropyridine calcium antagonist not only exhibits a blood pressure-lowering effect but also reduces ET-1-induced vasoconstriction and improves endothelium-dependent vasodilation. Those vasculoprotective effects may importantly contribute to a reduction in major clinical events seen during treatment with these compounds.
Authors:
Isabella Sudano; Agostino Virdis; Stefano Taddei; Lukas Spieker; Roberto Corti; Georg Noll; Antonio Salvetti; Thomas F Luscher
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2006-12-18
Journal Detail:
Title:  Hypertension     Volume:  49     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-19     Completed Date:  2007-02-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-90     Citation Subset:  IM    
Affiliation:
Cardiovascular Center, Cardiology, University Hospital of Zurich, Zurich, Switzerland. sudano@usz.ch
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / administration & dosage,  pharmacology
Adult
Brachial Artery
Calcium Channel Blockers / administration & dosage*,  therapeutic use
Delayed-Action Preparations
Dose-Response Relationship, Drug
Drug Administration Schedule
Endothelin-1 / administration & dosage,  pharmacology*
Female
Forearm / blood supply
Humans
Hypercholesterolemia / complications
Hypertension / complications,  drug therapy*,  physiopathology*
Injections, Intra-Arterial
Male
Middle Aged
Nifedipine / administration & dosage*,  therapeutic use
Phenylephrine / administration & dosage,  pharmacology
Regional Blood Flow / drug effects
Vasoconstriction / drug effects*
Vasoconstrictor Agents / administration & dosage,  pharmacology
Vasodilator Agents / administration & dosage,  pharmacology
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Delayed-Action Preparations; 0/Endothelin-1; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 21829-25-4/Nifedipine; 51-84-3/Acetylcholine; 59-42-7/Phenylephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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