title: Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness.
abstract: Rats with adenine-induced chronic renal failure (A-CRF) develop metabolic and cardiovascular abnormalities resembling those in patients with chronic kidney disease. The aim of this study was to investigate the mechanisms of hypertension in this model and to assess aortic stiffness in vivo. Male Sprague-Dawley rats were equipped with radiotelemetry probes for arterial pressure recordings and received either chow containing adenine or normal control diet. At 7 to 11 wk after study start, blood pressure responses to high NaCl (4%) diet and different pharmacological interventions were analyzed. Aortic pulse wave velocity was measured under isoflurane anesthesia. Baseline 24-h mean arterial pressure (MAP) was 101 ± 10 and 119 ± 9 mmHg in controls and A-CRF animals, respectively (P < 0.01). After 5 days of a high-NaCl diet, MAP had increased by 24 ± 6 mmHg in A-CRF animals vs. 2 ± 1 mmHg in controls (P < 0.001). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (-12 ± 3 vs. -5 ± 5 mmHg, P < 0.05). Aortic pulse wave velocity was elevated in A-CRF rats (5.10 ± 0.51 vs. 4.58 ± 0.17 m/s, P < 0.05). Plasma levels of creatinine were markedly elevated in A-CRF animals (259 ± 46 vs. 31 ± 2 μM, P < 0.001), whereas plasma renin activity was suppressed (0.6 ± 0.5 vs. 12.3 ± 7.3 μg·l(-1)·h(-1), P < 0.001). In conclusion, hypertension in A-CRF animals is characterized by low plasma renin activity and is aggravated by high-NaCl diet, suggesting a pathogenic role for sodium retention and hypervolemia probably secondary to renal insufficiency. Additionally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic pulse wave velocity.
authors.affiliation: Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Sweden. lisa.nguy@gu.se
authors.forename: Lisa
authors.initials: L
authors.lastname: Nguy
authors.forename: Maria E
authors.initials: ME
authors.lastname: Johansson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Grimberg
authors.forename: Jaana
authors.initials: J
authors.lastname: Lundgren
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
authors.forename: Jon O
authors.initials: JO
authors.lastname: Lundberg
authors.forename: Holger
authors.initials: H
authors.lastname: Nilsson
authors.forename: Gregor
authors.initials: G
authors.lastname: Guron
mesh_terms: D000225:Adenine / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006977:Hypertension, Renal / Q000209:etiology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000503:physiopathology*; D007677:Kidney Function Tests; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D013686:Telemetry; D013777:Tetrazoles / Q000494:pharmacology; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D009569:Nitric Oxide; D012083:Renin; D000225:Adenine; C081643:candesartan; D019331:NG-Nitroarginine Methyl Ester
keywords: adenine; aortic stiffness; chronic kidney disease; hypertension; pulse wave velocity