Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic threshold in patients with stable coronary disease.
BACKGROUND
Capsaicin has been shown to exert direct vasodilating effects through increased calcitonin gene-related peptide (CGRP) release. However, no data exist on its effect following systemic administration in humans.


METHODS
Twelve male patients with stable coronary disease and a persistently positive exercise were selected for study. According to a double blind, placebo-controlled, cross-over study, patients were randomized to placebo or 3 g oleic capsaicin-containing patches, on 2 different days and with a 2-day interval between treatments. Patients performed treadmill exercise testing according to the Bruce protocol. Time to 1 mm ST segment depression and to peak exercise, maximal ST segment depression, and the number of ECG leads showing diagnostic changes were also measured. Blood samples for nitric oxide (NO) and CGRP were drawn at baseline, 2, 6, and 24 hours after exercise.


RESULTS
On placebo, all patients had a positive ECG during exercise test. Only 1 patient experienced angina, on both treatments. With capsaicin, 1 patient had a negative exercise, while 8 patients significantly increased time to 1 mm ST depression from 328 +/- 167 to 401 +/- 174 seconds (P = 0.01). Of the remaining patients, 1 did not show any changes and 2 showed a worse ischemic threshold when on capsaicin. CGRP levels were not significantly different between placebo and capsaicin treatment. Conversely, when on capsaicin, NO significantly increased at 6 hours.


CONCLUSIONS
Transdermal capsaicin may improve ischemic threshold in patients with stable coronary disease, probably through arteriolar vasodilation. Increased capsaicin-induced NO availability could represent the principal mechanism of action.
Fragasso
Gabriele
G
Cardiologia Clinica, Istituto Scientifico/Universita' San Raffaele, Milano, Italy. gabriele.fragasso@hsr.it
Palloshi
Altin
A
Piatti
Pier Marco
PM
Monti
Lucilla
L
Rossetti
Enrico
E
Setola
Emanuela
E
Montano
Chiara
C
Bassanelli
Giorgio
G
Calori
Giliola
G
Margonato
Alberto
A
D000279:Administration, Cutaneous; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000097:blood; D002211:Capsaicin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D004562:Electrocardiography / Q000009:adverse effects; D005080:Exercise Test / Q000379:methods; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019301:Oleic Acid / Q000008:administration & dosage / Q000737:chemistry; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry; D013997:Time Factors
D014677:Pharmaceutical Vehicles; D019301:Oleic Acid; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin