title: Angiotensin II action in isolated microperfused rabbit afferent arterioles is modulated by flow.
abstract: We have recently presented evidence that endogenous nitric oxide (NO) and prostaglandins (PGs) modulate angiotensin II (Ang II) action in microperfused afferent arterioles (Af-Arts). Because flow may be a physiological stimulus of endothelial release of NO and PGs, we tested the hypothesis that flow through the lumen of the Af-Art stimulates the endothelium to produce NO and PGs, which in turn modulate the action of Ang II. We microdissected the terminal segment of an interlobular artery together with two Af-Arts, their glomeruli 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 Ang II action in free-flow and non-flow 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-flow vs. non-flow; N = 9). Disrupting the endothelium augmented Ang II action 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 between them (N = 8). Pretreatment with an inhibitor of either NO synthase (N-nitro-L-arginine methyl ester) or cyclooxygenase (indomethacin) augmented Ang II action more in free-flow than non-flow Af-Arts, likewise abolishing the differences between them. These results suggest that intraluminal flow modulates the vasoconstrictor action of Ang II in Af-Arts via endothelium-derived NO and PGs. Thus flow may be important in the fine control of glomerular hemodynamics.
authors.affiliation: Department of Internal Medicine and Heart and Vascular Institute, Henry Ford Hospital, Detroit, Michigan, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Juncos
authors.forename: Y
authors.initials: Y
authors.lastname: Ren
authors.forename: S
authors.initials: S
authors.lastname: Arima
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: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000378:metabolism; D005169:Factor VIII / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000166:cytology / Q000201:enzymology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion / Q000379:methods*; D011817:Rabbits; D012039:Regional Blood Flow
chemical_list: D016861:Cyclooxygenase Inhibitors; D000804:Angiotensin II; D005169:Factor VIII; D019001:Nitric Oxide Synthase; D009638:Norepinephrine; D007213:Indomethacin