Prolonged microvascular vasodilation induced by leukotriene B4 in human skin is cyclooxygenase independent.
When the potent chemoattractant leukotriene B4 (LTB4) is applied topically to human skin it causes delayed onset, long-lasting leukocyte accumulation and erythema. We investigated the role of prostaglandins in the increase in local blood flow by applying LTB4 topically to the forearm skin of 22 healthy male volunteers and measuring the effect of the anti-inflammatory compounds tenidap, naproxen and indomethacin. Local microvascular blood flow responses were measured by laser Döppler flow probe and planimetry. LTB4 induced dose-dependent increases in blood flow which were maximal at 48 hr and lasted 4 days. Laser Döppler flow (% flux) at 48 hr was 2.7 +/- 0.1, 20.6 +/- 3.1, 28.7 +/- 2.4 and 30.2 +/- 2.3% in control and 3, 10, 30 ng/site LTB4, respectively (mean +/- S.E.M.). In eight subjects the intradermal injection of indomethacin, at a dose (3 x 10(-9) mol/site) that inhibited significantly the increased flow induced by intradermally injected arachidonic acid (1 x 10(-9) mol/site, n = 6), had no effect on the increased skin blood flow response induced by LTB4 (10 ng/site) at 48 hr. Blood flow in vehicle-injected LTB4 sites was 810 +/- 150% above basal and 819 +/- 149% in sites injected with indomethacin. In 20 subjects, the effect of the anti-inflammatory drugs naproxen and tenidap given orally on the skin blood flow responses to LTB4 were compared in a double-blind crossover design. The 1085 +/- 98% increase in local blood flow induced by 30 ng of LTB4 at 48 hr was unaltered at the end of the treatment periods with either naproxen or tenidap, where blood flow in the LTB4-treated sites was increased 1018 +/- 131% and 1034 +/- 130%, respectively. Because the vasodilator response to exogenous LTB4 was not altered by nonsteroidal anti-inflammatory drugs either injected locally or taken orally, we suggest that endogenous prostaglandins are not involved in this response.
Larkin
S W
SW
Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
Fraser
L
L
Showell
H J
HJ
Williams
T J
TJ
Warren
J B
JB
D000284:Administration, Oral; D000287:Administration, Topical; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004890:Erythema / Q000139:chemically induced; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009288:Naproxen / Q000008:administration & dosage; D000078183:Oxindoles; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D007211:Indoles; D000078183:Oxindoles; D007975:Leukotriene B4; D016718:Arachidonic Acid; D009288:Naproxen; C062866:tenidap; D007213:Indomethacin