title: Endothelium-derived nitric oxide supports renin cell recruitment through the nitric oxide-sensitive guanylate cyclase pathway.
abstract: Chronic challenge of renin-angiotensin causes recruitment of renin-producing cells in the kidney along the media layer of afferent arterioles and hypertrophy of cells in the juxtaglomerular apparatus. This study aimed to define the role of nitric oxide (NO) with regard to the recruitment pattern of renin-producing cells and to the possible pathways along which NO could act. We considered the hypothesis that endothelium-derived NO acts via NO-sensitive guanylate cyclase. Mice were treated with low-salt diet in combination with the angiotensin I-converting enzyme inhibitor enalapril for 3 weeks, which led to a 13-fold increase in renin expression associated with marked recruitment of renin cells in afferent arterioles and hypertrophy of the juxtaglomerular apparatus in wild-type mice. In wild-type mice additionally treated with the nonselective NO synthase inhibitor L-NAME, the recruitment of renin-expressing cells along the afferent arterioles was absent and juxtaglomerular hypertrophy was diminished. An almost identical attenuation of renin cell recruitment as with L-NAME treatment in wild-type mice was found in mice lacking the endothelial isoform of NO synthase. Treatment of mice lacking NO-sensitive guanylate cyclase in renin-expressing cells and preglomerular smooth muscle cells with low-salt diet in combination with the angiotensin I-converting enzyme inhibitor enalapril for 3 weeks produced juxtaglomerular hypertrophy like in wild-type mice, but no recruitment in afferent arterioles. These findings suggest that endothelium-derived NO and concomitant formation of cGMP in preglomerular renin cell precursors supports recruitment of renin-expressing cells along preglomerular vessels, but not in the juxtaglomerular apparatus.
authors.affiliation: Institute of Physiology, University of Regensburg, Regensburg, Germany. bjoern.neubauer@vkl.uni-regensburg.de
authors.forename: Björn
authors.initials: B
authors.lastname: Neubauer
authors.forename: Katharina
authors.initials: K
authors.lastname: Machura
authors.forename: Ramona
authors.initials: R
authors.lastname: Kettl
authors.forename: Maria Luisa S Sequeira
authors.initials: ML
authors.lastname: Lopez
authors.forename: Andreas
authors.initials: A
authors.lastname: Friebe
authors.forename: Armin
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism*; D007606:Juxtaglomerular Apparatus / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D012083:Renin; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester