Inhibition of angiotensin-converting enzyme in human hand veins

• Published in: Clinical pharmacology and therapeutics Vol. 65; no. 1; pp. 58 - 65
• Main Authors: Chalon, Stephan, Bedarida, Gabriella V., Moreno, Heitor, Tejura, Bina, Urae, Akinori, Hoffman, Brian B., Blaschke, Terrence F.
• Format: Journal Article
• Language: English
• Published: New York, NY Nature Publishing 01-01-1999
• Subjects: Administration, Oral; Adult; Angiotensin-Converting Enzyme Inhibitors - administration & dosage; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Antihypertensive agents; Biological and medical sciences; Bradykinin - physiology; Captopril - administration & dosage; Captopril - pharmacology; Cardiovascular system; Dose-Response Relationship, Drug; Enalaprilat - administration & dosage; Enalaprilat - pharmacology; Female; Hand - blood supply; Humans; Male; Medical sciences; Pharmacology. Drug treatments; Reference Values; Time Factors; Vasoconstriction - drug effects; Vasodilation - drug effects; Veins - drug effects; Human; Healthy subject; Investigation method; Captopril; Enalaprilat; Vasoconstriction; Antihypertensive agent; Biological effect; Vein; Hand; ACE inhibitor
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1016/S0009-9236(99)70122-0

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 μg/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.
Clinical Pharmacology & Therapeutics (1999) 65, 58–65; doi: