title: Renal endothelial function is associated with the anti-proteinuric effect of ACE inhibition in 5/6 nephrectomized rats.
abstract: In healthy rats, the physiological variation of baseline endothelial function of intrarenal arteries correlates with the severity of renal damage in response to a subsequent specific renal injury. However, whether such a variation in endothelial function may also condition or predict the variable response to angiotensin-converting enzyme-inhibiting treatment in these individuals has not been addressed before. To study this, 5/6 nephrectomy was performed to induce renal injury and chronic kidney disease in a group of healthy Wistar rats. At the time of nephrectomy, interlobar arteries were obtained from the extirpated right kidney and studied in vitro for endothelium-dependent relaxation to acetylcholine. Six weeks thereafter, treatment with lisinopril was started (n = 11) and continued for 9 wk. Proteinuria (metabolic cages) and systolic blood pressure (SBP; tail cuff) were evaluated weekly, and these were analyzed in relation to renal endothelial function at baseline. 5/6 Nephrectomy induced an increase in SBP and progressive proteinuria. Treatment with lisinopril reduced SBP and slowed proteinuria, albeit to a variable degree among individuals. The acetylcholine-induced renal artery dilation at baseline negatively correlated with lisinopril-induced reduction of proteinuria (r(2) = 0.648, P = 0.003) and with the decrease in SBP (r(2) = 0.592, P = 0.006). Our data suggest that angiotensin-converting enzyme-inhibitor attenuates the progression of renal damage the most in those individuals with decreased basal renal endothelial-mediated vasodilation.
authors.affiliation: Unit of Nephrology Dialysis and Renal Transplantation, Fondazione Ca' Granda Ospedale Maggiore Policlinico di Milano, Milano, Italy; simone.vettoretti@policlinico.mi.it.
authors.forename: Simone
authors.initials: S
authors.lastname: Vettoretti
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovak Republic;
authors.forename: Peter
authors.initials: P
authors.lastname: Vavrinec
authors.affiliation: Department of Pathology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Ochodnicky
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Leo E
authors.initials: LE
authors.lastname: Deelman
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: De Zeeuw
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Rob H
authors.initials: RH
authors.lastname: Henning
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Buikema
mesh_terms: D000109:Acetylcholine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D066298:In Vitro Techniques; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use*; D009392:Nephrectomy; D011507:Proteinuria / Q000188:drug therapy; D011897:Random Allocation; D017208:Rats, Wistar; D012077:Renal Artery / Q000187:drug effects; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy*; D014664:Vasodilation
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril; D000109:Acetylcholine
keywords: ACEi treatment; chronic kidney disease; endothelial function; proteinuria; response variability