Absence of potentiation of the skin response to intradermal bradykinin by a long-acting angiotensin converting enzyme inhibitor, trandolapril, at conventional antihypertensive dosage in human volunteers: a double-blind, randomized, cross-over, placebo-controlled trial.
A double-blind, randomized, cross-over, placebo-controlled study was carried out to determine the extent and duration of potentiation of the action of bradykinin introduced intradermally by a long-acting novel angiotensin converting enzyme (ACE) inhibitor, trandolapril. The investigations were performed in a temperature and humidity-controlled laboratory. Intradermal injections of 1 microgram, 2.5 micrograms and 5 micrograms of bradykinin and normal saline (as control) were made into the forearm skin of eight healthy normotensive male volunteers aged 21-33 years (mean 28 years) at baseline, 2, 4, 8, 24, 48, 72 and 96 hours after either 2 mg trandolapril or placebo given orally. Skin blood flow outside the induced weal was monitored by laser Doppler flowmetry (mean of recordings at four sites adjacent to the weal within the flare area). Flare area and weal volume were also measured. Trandolapril reduced the mean arterial pressure. However, there was no evidence that this activity was associated with a potentiation of the cutaneous action of bradykinin. In conclusion, it would appear that potentiation of the action of bradykinin may not be an important contributing factor to the fall in total peripheral vascular resistance associated with ACE inhibition in humans in the control of hypertension.
Li Kam Wa
T C
TC
Department of Clinical Pharmacology, St Bartholomew's Hospital, West Smithfield, London, UK.
Cooke
E D
ED
Beacham
J
J
Turner
P
P
D000284:Administration, Oral; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004357:Drug Synergism; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007271:Injections, Intradermal; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D001920:Bradykinin