title: Interaction of angiotensin II and nitric oxide in isolated perfused afferent arterioles of mice.
abstract: The present study was performed to evaluate angiotensin II (Ang II)-nitric oxide (NO) interaction in afferent arterioles (Af) of wild-type mice and mice that are homozygous (-/-) for disruption of the endothelial NO synthase (eNOS) gene. Af were microperfused, and the dose responses were assessed for the NO precursor L-arginine (n = 4), NO inhibitor NG-nitro-L-arginine methyl ester (L-NAME, n = 5), L-NAME after pretreatment with L-arginine (n = 5), Ang II (n = 8), and Ang II after pretreatment with L-NAME (n = 7). Acute administration of L-arginine and L-NAME (both in doses from 10(-6) to 10(-3) mol/L) did not change arteriolar diameter. Moreover, pretreatment with L-arginine did not change the response to L-NAME. However, Ang II, applied in doses of 10(-12), 10(-10), 10(-8), and 10(-6) mol/L, significantly reduced the lumen to 66.5 +/- 7.0% and 62.2 +/- 8.0% at 10(-8) and 10(-6) mol/L Ang II, respectively. The contraction was augmented after L-NAME pretreatment (19.5 +/- 13.6% and 25.5 +/- 10.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). In eNOS (-/-) mice (n = 8), the response to Ang II also was enhanced (9.1 +/- 6.0% and 11.2 +/- 8.2% at 10(-8) and 10(-6) mol/L Ang II, respectively). Female mice did not differ from male mice in their reactivity to Ang II (n = 9) and Ang II + L-NAME pretreatment (n = 11). The study shows that (1) it is feasible to microperfuse mouse Af, (2) the basal production of endothelial NO is very low and not inducible by L-arginine in Af of mice, and (3) a counteracting effect of NO is initiated by Ang II. High Ang II sensitivity in eNOS (-/-) mice underscores the considerable role of endothelial-derived NO to balance Ang II vasoconstriction in Af.
authors.affiliation: Johannes-Müller-Institute of Physiology, Humboldt-University of Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
authors.affiliation: Johannes-Müller-Institute of Physiology, Humboldt-University of Berlin, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Mrowka
authors.affiliation: Johannes-Müller-Institute of Physiology, Humboldt-University of Berlin, Berlin, Germany.
authors.forename: Eberhard
authors.initials: E
authors.lastname: Storch
authors.affiliation: Department of Nephrology, University-Hospital Charité, Humboldt-University of Berlin, Berlin, Germany.|Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Hocher
authors.affiliation: Johannes-Müller-Institute of Physiology, Humboldt-University of Berlin, Berlin, Germany.
authors.forename: Pontus B
authors.initials: PB
authors.lastname: Persson
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010477:Perfusion; D018709:Statistics, Nonparametric; D014661:Vasoconstriction / Q000187:drug effects; D014743:Videotape Recording
chemical_list: D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester