title: Flow modulates myogenic responses in isolated microperfused rabbit afferent arterioles via endothelium-derived nitric oxide.
abstract: Flow may be a physiological stimulus of the endothelial release of nitric oxide (NO) and prostaglandins (PGs). We tested the hypothesis that pressure-induced constriction of the glomerular afferent arteriole (Af-Art) is modulated by luminal flow via endothelial production of NO. We microdissected the terminal segment of an interlobular artery together with two Af-Arts, their glomeruli (GL) and efferent arterioles (Ef-Art). The two Af-Arts were perfused simultaneously from the interlobular artery, while one Ef-Art was occluded. Since the arteriolar perfusate contained 5% albumin, oncotic pressure built up in the glomerulus with the occluded Ef-Art and opposed the force of filtration, resulting in little or no flow through the corresponding Af-Art. Thus this preparation allowed us to observe free-flow and no-flow Af-Arts simultaneously 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 whether flow modulates myogenic constriction through endothelium-derived NO and/or PGs, we examined pressure-induced constriction before and after (a) disruption of the endothelium, (b) inhibition of NO synthesis with NW-nitro-L-arginine methyl ester (L-NAME), or (c) inhibition of cyclooxygenase with indomethacin. Both endothelial disruption and L-NAME augmented pressure-induced constriction in free-flow but not no-flow Af-Arts, abolishing the differences between the two. However, indomethacin had no effect in either free-flow or no-flow Af-Arts. These results suggest that intraluminal flow attenuates pressure-induced constriction in Af-Arts via endothelium-derived NO. Thus flow-stimulated NO release may be important in the fine control of glomerular hemodynamics.
authors.affiliation: Department of Internal Medicine, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Juncos
authors.forename: J
authors.initials: J
authors.lastname: Garvin
authors.forename: O A
authors.initials: OA
authors.lastname: Carretero
authors.forename: S
authors.initials: S
authors.lastname: Ito
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000502:physiology*; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology; D011817:Rabbits; D012039:Regional Blood Flow; D014661:Vasoconstriction
chemical_list: D011453:Prostaglandins; D009569:Nitric Oxide; D007213:Indomethacin