title: Control of renin secretion from kidneys with renin cell hyperplasia.
abstract: In states of loss-of-function mutations of the renin-angiotensin-aldosterone system, kidneys develop a strong hyperplasia of renin-producing cells. Those additional renin cells are located outside the classic juxtaglomerular areas, mainly in the walls of preglomerular vessels and most prominently in multilayers surrounding afferent arterioles. Since the functional behavior of those ectopic renin cells is yet unknown, we aimed to characterize the control of renin secretion from kidneys with renin cell hyperplasia. As a model, we used kidneys from mice lacking aldosterone synthase (AS⁻/⁻ mice), which displayed 10-fold elevations of renin mRNA and plasma renin concentrations. On the absolute level, renin secretion from isolated AS⁻/⁻ kidneys was more than 10-fold increased over wild-type kidneys. On the relative level, the stimulation of renin secretion by the β-adrenergic activator isoproterenol or by lowering of the concentration of extracellular Ca²⁺ was very similar between the two genotypes. In addition, the inhibitory effects of ANG II and of perfusion pressure were similar between the two genotypes. Deletion of connexin40 blunted the pressure dependency of renin secretion and the stimulatory effect of low extracellular Ca²⁺ on renin secretion in the same manner in kidneys of AS⁻/⁻ mice as in wild-type mice. Our findings suggest a high degree of functional similarity between renin cells originating during development and located at different positions in the adult kidney. They also suggest a high similarity in the expression of membrane proteins relevant for the control of renin secretion, such as β₁-adrenergic receptors, ANG II type 1 receptors, and connexin40.
authors.affiliation: Physiologisches Institut, Universität Regensburg, Universitätsstrasse 31, Regensburg D-93053, Germany. armin.kurtz@ur.de.
authors.forename: Birgül
authors.initials: B
authors.lastname: Kurt
authors.forename: Christian
authors.initials: C
authors.lastname: Karger
authors.forename: Charlotte
authors.initials: C
authors.lastname: Wagner
authors.forename: Armin
authors.initials: A
authors.lastname: Kurtz
mesh_terms: D000818:Animals; D017630:Connexins / Q000096:biosynthesis; D019405:Cytochrome P-450 CYP11B2 / Q000172:deficiency; D005260:Female; D006965:Hyperplasia / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D012083:Renin / Q000096:biosynthesis / Q000378:metabolism*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D019405:Cytochrome P-450 CYP11B2; D007545:Isoproterenol; D012083:Renin; D000097003:Gap Junction alpha-5 Protein
keywords: aldosterone synthase knockout; isolated perfused kidney; renin cell hyperplasia; renin secretion