FLOW MODULATES MYOGENIC RESPONSES IN ISOLATED MICROPERFUSED RABBIT AFFERENT ARTERIOLES VIA ENDOTHELIUM-DERIVED NITRIC-OXIDE

Flow may be a physiological stimulus of the endothelial release of nit ric oxide (NO) and prostaglandins (PGs). We tested the hypothesis that pressure-induced constriction of the glomerular afferent arteriole (A f-Art) is modulated by luminal flow via endothelial production of NO, We microdissected the terminal segment of an interlobular artery toget her with two Af-Arts, their glomeruli (GL) and efferent arterioles (Ef -Art). The two Af-Arts were perfused simultaneously from the interlobu lar artery, while one Ef-Art was occluded. Since the arteriolar perfus ate contained 5% albumin, oncotic pressure built up in the glomerulus with the occluded Ef-Art and opposed the force of filtration, resultin g in little or no flow through the corresponding Af-Art. Thus this pre paration allowed us to observe free-flow and no-few Af-Arts simultaneo usly during stepwise 30-mmHg increases in intraluminal pressure (from 30 to 120 mmHg). Pressure-induced constriction was weaker in free-flow than no-flow Af-Arts, with the luminal diameter decreasing by 11.1+/- 1.7 and 25.6+/-2.3% (n = 30), respectively, at 120 mmHg. To examine wh ether how modulates myogenic constriction through endothelium-derived NO and/or PGs, we examined pressure-induced constriction before and af ter (a) disruption of the endothelium, (b) inhibition of NO synthesis with N-w-nitro-L-arginine methyl ester (L-NAME), or (c) inhibition of cyclooxygenase with indomethacin. Both endothelial disruption and L-NA ME augmented pressure-induced constriction in free-flow but not no-flo w Af-Arts, abolishing the differences between the two. However, indome thacin had no effect in either free-flow or no-flow Af-Arts. These res ults suggest that intraluminal how attenuates pressure-induced constri ction in Af-Arts via endothelium-derived NO. Thus flow-stimulated NO r elease may be important in the fine control of glomerular hemodynamics .