ANGIOTENSIN-II ACTION IN ISOLATED MICROPERFUSED RABBIT AFFERENT ARTERIOLES IS MODULATED BY FLOW

We have recently presented evidence that endogenous nitric oxide (NO) and prostaglandins (PGs) modulate angiotensin II (Ang II) action in mi croperfused afferent arterioles (Af-Arts). Because flow may be a physi ological stimulus of endothelial release of NO and PGs, we tested the hypothesis that flow through the lumen of the Af-Art stimulates the en dothelium to produce NO and PGs, which in turn modulate the action of Ang II. We microdissected the terminal segment of an interlobular arte ry together with two Af-Arts, their glomeruli and efferent arterioles (Ef-Art). The two Af-Arts were perfused simultaneously from the interl obular artery, while one Ef-Art was occluded. Since the arteriolar per fusate contained 5% albumin. oncotic pressure built up in the glomerul us with the occluded Ef-Art and opposed the force of filtration, resul ting in little or no flow through the corresponding Af-Art. Thus this preparation allowed us to observe Ang II action in free-flow and non-f low Af-Arts simultaneously. Ang II-induced constriction was weaker in free-flow than non-flow Af-Arts, with the luminal diameter decreasing by 8 +/- 2% and 23 +/- 3% at 10(-9) M, respectively (P < 0.013 free-fl ow vs. non-flow: N = 9). Disrupting the endothelium augmented Ang II a ction in free-flow (33 +/- 5.1%; P < 0.01 vs. intact endothelium) but not non-flow Af-Arts (31 +/- 5.3%), thus abolishing the differences be tween them (N = 8). Pretreatment with an inhibitor of either NO syntha se (N-nitro-L-arginine methyl ester) or cyclooxygenase (indomethacin) augmented Ang II action more in free-flow than non-flow Af-Arts, likew ise abolishing the differences between them. These results suggest tha t intraluminal flow modulates the vasoconstrictor action of Ang II in Af-Arts via endothelium-derived NO and PGs. Thus how may be important in the fine control of glomerular hemodynamics.