PLATELET-ACTIVATING-FACTOR DILATES EFFERENT ARTERIOLES THROUGH GLOMERULUS-DERIVED NITRIC-OXIDE

Despite evidence that platelet-activating factor (PAF) is produced by the glomerulus, its direct action on the glomerular microcirculation i s poorly understood. It was recently reported that at picomolar concen trations, PAF dilates isolated microperfused afferent arterioles (Af-A rt) via nitric oxide (NO). The present study tested the hypothesis tha t PAF acts on the glomerulus to release NO, which in turn controls the resistance of the efferent arteriole (Ef-Art). Rabbit Ef-Art were per fused from the distal end (retrograde perfusion (RP)) to eliminate the influence of the glomerulus, or through the glomerulus from the end o f the Af-Arf (orthograde perfusion (OP)) to maintain the influence of the glomerulus. Ef-Art were preconstricted by approximately 40% with n orepinephrine and increasing doses of PAF were added to both the arter iolar perfusate and bath. Only with OP did PAF at picomolar concentrat ions cause significant dilation: at 400 pmol, the diameter increased b y 64 +/- 11% from the preconstricted level (N = 6, P < 0.01). This dil ation was completely abolished by pretreatment with an NO-synthesis in hibitor. To study its possible constrictor action, PAF was added to no npreconstricted Ef-Art. At nanomolar concentrations, PAF constricted E f-Art similarly in both RP and OP: at 40 nM, the diameter decreased by 24 +/- 4% (N = 6, P < 0.01) and 20 +/- 2% (N = 6, P < 0.01), respecti vely. This constriction was attenuated by pretreatment with indomethac in (Indo) in both RP (14 +/- 2%, N = 7; P< 0.02 versus without Indo) a nd OP (10 +/- 2%, N = 6; P< 0.02 versus without Indo). In conclusion: (1) at picomolar concentrations, PAF stimulates the glomerulus to rele ase NO, which in turn dilates the Ef-Art; and (2) at nanomolar concent rations, PAF constricts the Ef-Art partly through release of cyclooxyg enase metabolites. Thus, PAF may play a role in glomerular hemodynamic s under various physiological and pathological conditions.