Prolonged effect of CGRP in Raynaud's patients: a double-blind randomised comparison with prostacyclin.
1. Calcitonin gene related peptide (CGRP) is a potent endogenous vasodilator to which we have previously demonstrated a specific hypersensitivity in skin blood flow in the hands in patients with Raynaud's disease. 2. We have now investigated whether long infusion of CGRP can relieve symptoms of patients with Raynaud's disease using prostacyclin as a control. 3. Six patients were randomised to receive intravenous infusion of either human alpha-CGRP on one occasion, or prostacyclin (PGI2) on another occasion in a double-blind and cross-over design. The dose of each agent was initially titrated up to 8 ng kg-1 min-1 or to a maximum increase in heart rate of 25 beats min-1. 4. In addition to blood pressure, heart rate and skin blood flow measurements, infrared thermography and cold stress challenge was performed before, immediately after infusion and at 3 and 14 days post-infusion. 5. CGRP caused an increase in hand skin blood flow throughout its infusion, whilst PGI2 caused only a short lived increase. The thermographic results showed significant improvement in hand rewarming 3 days after CGRP but not after PGI2. 6. We conclude that 3 h infusion of CGRP was better tolerated than PGI2 and caused objective improvement up to 3 days. CGRP may be an alternative to PGI2 in some patients.
Shawket
S
S
Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge.
Dickerson
C
C
Hazleman
B
B
Brown
M J
MJ
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000627:therapeutic use*; D003080:Cold Temperature / Q000009:adverse effects; D004311:Double-Blind Method; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D005483:Flushing / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D011928:Raynaud Disease / Q000188:drug therapy* / Q000503:physiopathology; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply; D013312:Stress, Physiological / Q000503:physiopathology
D011464:Epoprostenol; D015740:Calcitonin Gene-Related Peptide