Different classes of PAF-antagonists block norepinephrine-induced vascular escape and tachyphylaxis in the isolated rabbit kidney

In order to study the role of platelet activating factor (PAF) on norepinephrine induced vascular escape and tachyphylaxis, compounds from different pharmacological families sharing PAF-antagonistic activity, were infused in the isolated rabbit kidney perfused with Krebs-Henseleit solution. A natural compound derived from Ginkgo biloba (BN 52020, 1.1 x 10(-6) M), a triazolobenzodiazepine substance (WEB 2170, 1.1 x 10(-6) M) and a dihydropyridine derivative lacking cardiovascular effects (PCA 4248, 2.7 x 10(-6) M), were analysed. The vascular reactivity to three cycles of norepinephrine (1.3 x 10(-6) M), infused in the kidneys treated with each of the PAF- antagonists, were evaluated for vascular escape and tachyphylaxis. The results demonstrated a significant reduction of both regulatory phenomena. A fall in renal vascular escape promoted by PAF antagonists, from a control level of 50.32 +/- 4.61 to 27.64 +/- 8.01% (p0.05), suggests a role for PAF-acether in the vascular adjustment of the mammalian kidney.