GLOMERULAR PROSTAGLANDINS MODULATE VASCULAR REACTIVITY OF THE DOWNSTREAM EFFERENT ARTERIOLES

Glomerular prostaglandins modulate vascular reactivity of the down stream efferent arterioles. The balance of vascular resistance in afferent (Af-) and efferent arterioles (Ef-Arts) is a crucial factor that determines glomerular hemodynamics. We have recently reported that when Ef-Arts were perfused from the distal end of the Af-Art through the glomerulus (orthograde perfusion; OF), both angiotensin II (Ang II) and norepinephrine (NE) induced much weaker constriction than they did when Ef-Arts were perfused from the distal end (retrograde perfusion; RP). This difference was not affected by inhibiting synthesis of nitric oxide. In the present study, we tested the hypothesis that glomerular prostaglandins (PGs) may modulate vascular reactivity of the downstream Ef-Art. In addition, we examined the possible modulatory role of PGs in the Af-Art responses to Ang II or NE, Both Ang II and NE caused dose-dependent constriction of Ef-Arts with either OP or RP; however, the constriction was stronger in RP. At 10(-8) M, Ang II decreased Ef-Art diameter by 35 +/- 3.5% in OP (N = 9) compared to 73 +/- 3.9% in RP (N = 5), while 10(-6) M NE decreased the diameter by 25 +/- 3.6% in OP (N = 9) compared to 62 +/- 7.2% in RP (N = 5). Pretreatment with 5 x 10(-5) M indomethacin (Indo) did not alter basal diameter with either method of perfusion. However, in OP it significantly augmented the constriction induced by Ang II and NE; 10(-8) M Ang II and 10(-6) M NE now decreased the diameter by 72 +/- 4.7% (N = 8; P < 0.01 vs, non-treated) and 48 +/- 3.3% (N = 7; P < 0.01), respectively. In contrast, Indo had no effect on either Ang II- or NE-induced constriction in Ef-Arts with RP. In vehicle-treated Af-Arts, Ang II had no effect until the concentration reached 10(-9) M, whereas it began to cause significant constriction at concentrations as low as 10(-11) M in Indo-treated Af-Arts. These results suggest that the resistance of the Ef-Art may be regulated by PGs released by the upstream glomerulus, while PGs synthesized within the Af-Art may modulate Ang II action in the Af-Art.