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Priming interactions between platelet activating factor and histamine in the in vivo microcirculation

To elucidate whether priming exists between platelet‐activating factor (PAF) and histamine in the microcirculation, we measured the clearance of FITC‐dextran 150 in response to the topical applications of sub‐stimulatory concentrations of PAF and histamine. Maximal priming by PAF was observed when a 5‐min interval separated the applications of 10–9m PAF and 10–6m histamine. The mean (± SEM) clearance resulting from this sequence of agonist administration was 7529 ± 659 nl·2 h–1·g–1, representing a 4.5‐fold enhancement in FITC‐dextran 150 clearance compared with that evoked by 10–6m histamine alone (1664 ± 397 nl·2 h–1·g–1). Lowering the PAF priming dose to 10–11m, or reversing the order of agonist addition to the microcirculation, resulted in diminished but significant responses of 3545 ± 1143 and 4467 ± 1170 nl·2 hr–1·g–1, respectively. Coapplication of PAF and histamine or increasing the time interval between the agonists to 15 min greatly reduced the responses to 1906 ± 678 and 2770 ± 837, respectively. The PAF receptor antagonist WEB 2086 (2 mg/kg i.v.), the H1 blocker pyrilamine (10 mg/kg i.v.), and leukocyte depletion with cyclophosphamide (150 mg/kg i.p.) completely abolished the PAF priming effect. In addition, the 5‐lipoxygenase inhibitor RG 5901 (1 or 10 mg/kg i.v.) produced a two‐thirds attenuation in PAF priming. We conclude that 1) PAF has the ability to prime the in vivo microvascular actions of histamine in both a concentration and time‐dependent fashion; 2) this primed response is receptor mediated; and 3) histamine can prime the microcirculation for enhanced responses to PAF. Our data also demonstrate that leukocytes and the release of leukotrienes participate in PAF priming.—Tomeo, A. C.; Egan, R. W.; Durán, W. N. Priming interactions between platelet‐activating factor and histamine in the in vivo microcirculation. FASEB J. 5: 2850‐2855; 1991.