A new technique for ranking vascular corticosteroid effects in humans using laser-Doppler velocimetry.
By combining laser-Doppler velocimetry with reactive hyperemia, induced by arterial occlusion of 4-min duration we have established a simple and atraumatic new ranking technique for assessing steroid potency. The experiments were performed in 19 healthy volunteers. Budesonide (Preferid) and placebo (vehicle) were applied under occlusion on the flexor aspect of the forearm for 2, 24, and 48 h. Blood flow was measured with a laser-Doppler flowmeter before and after arterial occlusion with a blood pressure cuff on the upper arm. The induced reactive hyperemia reaction was measured planimetrically on the registered curves. The steroid preparation caused a significant reduction of the hyperemia closely related to the application time. The reduction of the hyperemia was confirmed using the atraumatic 133Xe washout technique. In another group, hydrocortisone, hydrocortisone-butyrate (Locoid), budesonide (Preferid), and klobetasol (Dermovat) applied under occlusion for 1 h were compared. A significant dose-response relation corresponding to the expected rank-order efficacy was revealed. In 10 experiments, pretreatment with 50 mg indomethacin i.v. resulted in a significant reduction of the hyperemia reaction. As a hypothesis we therefore suggest that the reactive hyperemia reaction amplifies the vascular events and unmasks steroid-induced inhibition of the synthesis of arachidonic acid metabolites.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007834:Lasers; D008297:Male; D008875:Middle Aged; D011453:Prostaglandins / Q000096:biosynthesis; D012212:Rheology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects
D000305:Adrenal Cortex Hormones; D011453:Prostaglandins