Hypertension - experimental models

Nephrology Dialysis Transplantation 28 (Supplement 1): i325–i330, 2013 doi:10.1093/ndt/gft128 HYPERTENSION - EXPERIMENTAL MODELS MP084 GONADECTOMY PREVENTS THE INCREASE IN BLOOD PRESSURE AND SERUM ACE ACTIVITY IN ACE2 KNOCKOUT DIABETIC MALE MICE Sergi Clotet1, María José Soler1, Marta Rebull1, Julio Pascual1 and Marta Riera1 1 Department of Nephrology Hospital del Mar - IMIM Barcelona Spain Introduction and Aims: Whereas ACE2 deletion worsens kidney injury; its amplification ameliorates diabetic nephropathy. We previously showed that circulating ACE2 activity is increased in male diabetic NOD mice. The effect of gonadectomy in diabetic ACE2 knockout (ACE2KO) male mice has not been previously studied. Methods: We study the effect of ACE2 deletion on systolic blood pressure (SBP), urinary albumin excretion (UAE), kidney to body weight ratio (KW/BW) and serum (s) and kidney (k) ACE enzymatic activity in c57bl/6 streptozotocin (STZ)-induced male mice and their respective controls. We also evaluated the effect of gonadectomy in diabetic ACE2KO mice. Mice were followed-up for 19 weeks after induction of diabetes with STZ injection. Citrate was administered as a vehicle (cont). Study groups: ACE2KO-cont, ACE2KO-STZ, gonadectomy before diabetes induction GDX-ACE2KO-STZ. Results: Hyperglycemia was observed in all groups given STZ. KW/BW and UAE were increased in both diabetic wildtype (WT) (UAE 12-fold) and ACE2KO mice (UAE 27-fold). ACE2KO diabetic mice had increased SBP compared to diabetic WT. In addition, gonadectomized diabetic ACE2KO showed significantly lower values of blood glucose, SBP, UAE, KW/BW compared to non-gonadectomized diabetic ACE2KO. Circulating ACE activity positively correlated with SBP (r=0.28; p=0.04) and was significantly increased in WT diabetic mice compared with WT-cont. Circulating ACE activity was increased in ACE2KO control mice as compared to WT control mice. Gonadectomy significantly decreased circulating ACE activity in diabetic ACEKO mice. In contrast, renal ACE activity was significantlyreduced in diabetic ACE2KO and WT animals. Conclusions: In ACE2KO mice circulating ACE activity was increased as compared to WT mice. In addition, in diabetic ACE2KO mice SBP was increased compared to diabetic WT mice. Gonadectomy reduced blood glucose, UAE, renal hypertrophy, blood pressure and circulating ACE activity. MP085 MYOCARDIAL AND RENAL REMODELING IN MALE WISTAR RATS RECEIVING HIGH SALT DIET Anatoly G. Kucher1, Marina M. Parastaeva1, Olga N. Beresneva1, Galina T. Ivanova2, Mikhail I. Zaraysky1, Antonina V. Artemeva1, Ivan G. Kaukov1 and Alexey V. Smirnov1 1 Institute of Nephrology St.-Petersburg State Pavlov Medical University St.-Petersburg Russian Federation, 2Laboratory of Clinical and Experimental Cardiology Pavlov Institute of Physiology St.-Petersburg Russian Federation Introduction and Aims: Myocardium, kidney and vasculature, in particular, reacts to changes in dietary NaCl intake through a complex series of events that are independent of blood pressure. The aim of this study was to compare the effect of normal and high NaCl content in the diet on the remodeling of the heart and kidney, and the NFκB expression in the myocardium in rats. Methods: The study was performed in male Wistar rats. Control group (C) of animals (n=8) received normal NaCl intake (0.34%), experimental (E; n=8) – high (8%). Experimental period was 8 weeks. Mean BP was measured in awaked rats by tail cuff method. Serum urea (Ur), creatinine (Cr), total calcium and sodium levels were determined. Daily volume of urine and concentration of sodium in the urine was also determined. The degree of left ventricular hypertrophy was estimated as a ratio: left ventricular mass/body mass (LVH; mg/g). The degree of left (LKH) and right (RKH) kidneys hypertrophy was estimated as a ratio: kidney mass/body mass, mg/g). Determination of NFkB expression relative level in myocardium was performed under the semi-quantitative protocol. The obtained results were normalized by the expression level of reference gene GAPDH and compared between control and experimental myocardium with the use of 2-ΔΔCt method. Results: High salt intake does not lead significant rise (mean±SE) of BP (135±5 mmHg) compared with C (130±5 mmHg). There are no difference in concentrations of Ur (6.2±0.5 mmol/l in C vs5.6±0.8 mmol/l in E), Cr (0.044±0.01mmol/l in C vs 0.038 ±0.02 mmol/l in E). calcium and sodium in the blood serum between groups. High intake of NaCl produced a significant increase in urinary excretion of sodium (434.6 ±67.4 mmol/l vs 89.4±10.3 mmol/l – in C, p <0.001) in the absence of significant distinction of daily volume of urine between groups. Consumption of a diet with the high intake of NaCl was accompanied by increase of weight of left and right kidneys: the LKH was 3.51±0.07 mg/g (vs 2.97±0.08 mg/g – in C, p<0.01), the RKH – 3.65±0.05 mg/g (vs3.05±0.07 mg/g – in C, p<0.01). No significant differences in LVH could be detected among the groups (3.12±0.12 mg/g in C vs 3.01±0.09 mg/g in E). On the other hand high NaCl diet was accompanied by increase activity of the NFκB. Relative level of NFκB gene expression in E was in 3.4 times higher than in C. Conclusions: Consumption during the 2 months of a diet high in NaCl, without causing a rise in BP in Wistar rats leads to an increase in mass of the kidneys and the activation of NFκB in the myocardium, which may be one of the ways of myocardial remodeling and fibrosis. MP086 EFFECTS OF CHYMOSTATIN, A CHYMASE INHIBITOR, ON BLOOD PRESSURE AND KIDNEY HAEMODYNAMICS IN DIFFERENT MODELS OF HYPERTENSION IN THE RAT Malwina Roszkowska-Chojecka1, Agnieszka Walkowska1, Olga Gawrys1, Krzysztof Olszyński1 and Elzbieta Kompanowska-Jezierska1 1 Department of Renal and Body Fluid Physiology Mossakowski Medical Research Centre, Polish Academy of Sciences Warsaw Poland Introduction and Aims: Chymase is known to form angiotensin II in cardiovascular and renal tissues independent ofangiotensin-converting enzyme (ACE), and its expression is increased in pathological conditions. It was proposed that chymase inhibitors could be applied to inhibit the local renin-angiotensin systems (RAS) and possibly prevent the development of cardiovascular diseases. In this study we examined how blockade of chymase activity would affect blood pressure and renal haemodynamic parameters in different models of experimental hypertension. Methods: Male spontaneously hypertensive rats (SHR) in the development (age:7 weeks) and established stage of hypertension (16 weeks), male Sprague-Dawley rats with hypertension induced by stenosis of the renal artery performed 28 days before acute experiments (2K1C), and Sprague-Dawley rats with hypertension induced by unilateral nephrectomy followed by exposure to high sodium diet (4% Na w/w) for two weeks, were used.In acute experiments rats of all groups were anaesthetised with sodium thiopental, 100 mg/kg i.p. Mean arterial pressure (MAP) was r (...truncated)