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PMID: 9951431 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Inhibition of angiotensin-converting enzyme in human hand veins.

Clinical pharmacology and therapeutics ·Vol. 65 ·No. 1 ·1999-01-00 ·Pages 58-65

Chalon S, Bedarida GV, Moreno H, Tejura B, Urae A, Hoffman BB, Blaschke TF

Abstract

Conversion of angiotensin I to angiotensin II likely occurs in human veins, supporting the existence of endothelial angiotensin-converting enzyme (ACE) activity in these vessels. Using the dorsal hand vein technique, we investigated the effects of 2 ACE inhibitors, captopril (single oral dose of 6.25 mg) and enalaprilat (local infusion of 1 microgram/min), on venous responsiveness in healthy subjects. Orally administered captopril induced a marked decrease in angiotensin I- but not angiotensin II-induced venoconstriction. This blunted response persisted for at least 4 hours. Enalaprilat and captopril increased the sensitivity to bradykinin, decreasing the dose producing half-maximal response (ED50) of bradykinin 18-fold and 5-fold, respectively, without changing the maximal venodilatory response. These results confirm that there is substantial rapid metabolism of angiotensin I in human veins and suggest that a single dose of locally infused angiotensin I can be used with the dorsal hand vein technique to assess the time-course effect of vascular ACE inhibition after oral administration. Our findings also extend previous in vitro observations in human veins by showing that these agents potentiate the venodilatory effects of bradykinin in vivo.

MeSH Terms
Administration, Oral Adult Angiotensin-Converting Enzyme Inhibitors/administration & dosage,pharmacology Bradykinin/physiology Captopril/administration & dosage,pharmacology Dose-Response Relationship, Drug Enalaprilat/administration & dosage,pharmacology Female Hand/blood supply Humans Male Reference Values Time Factors Vasoconstriction/drug effects Vasodilation/drug effects Veins/drug effects
Chemicals
Angiotensin-Converting Enzyme Inhibitors Captopril Enalaprilat Bradykinin
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chalon S
Department of Medicine, Stanford University School of Medicine, CA, USA.
Bedarida G V
Moreno H
Tejura B
Urae A
Hoffman B B
Blaschke T F
Article Info
Journal
Clinical pharmacology and therapeutics
Abbr.
Clin Pharmacol Ther
ISSN
0009-9236
Published
1999-01-00
Pages
58-65
Language
English
Region
United States
NLM ID
0372741
Subset
IM
Grants
NIA NIH HHS · AG05627 · United States
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