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Effects of ACEI and low sodium intake on the renin–angiotensin system in mice with unilateral hydronephrosis
Abstracts
monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and endothelin-1 (ET-1) were determined by real time PCR. The expression of ED-1, transforming growth factor-β (TGF-β), and connective tissue growth factor (CTGF) was determined in the kidney by semiquantitative immunoblotting and immunohistochemistry. In DSH rats, SBP was increased, which was not affected by rosuvastatin treatment. Creatinine clearance was decreased while UAE was increased in DSH rats compared with controls, which were attenuated by rosuvastatin treatment. Glomerulosclerosis and tubulointerstitial fibrosis in DSH rats were attenuated by rosuvastatin treatment. The mRNA expression of MCP-1, ICAM-1, and ET-1 was increased in DSH rats, which was attenuated by rosuvastatin treatment. The expression of ED-1, TGF-β, and CTGF was increased in the kidney of DSH rats, which was counteracted by rosuvastatin treatment. Rosuvastatin is effective in preventing progression of renal injury in DSH rat, the mechanism of which is associated with anti-inflammatory and anti-fibrotic effects. doi:10.1016/j.ijcard.2009.09.311 KI000150 Control of hypertension in chronic renal failure patients VENU MADHAV KONALA, ADARSH BABU, DAVID EADINGTON Hull Royal Infirmary, United Kingdom Objective: Hypertension is one of the important independent risk factors in patients with chronic renal failure. Control of hypertension is essential to slow the cardiovascular risk, stroke and progression of renal disease. Various studies have indicated that hypertension control in patients with chronic kidney disease is poor, even though the awareness is high. This study aimed to look at control of hypertension in patients with chronic kidney disease stages 3 and 4. Design and method: A cross sectional observational study of 100 patients attending pre-dialysis clinic in the year 2007 at a United Kingdom tertiary hospital were randomly selected. We recorded the average blood pressure readings and the cause of hypertension. Number and type of anti-hypertensive medications were also recorded. Renal Association, United Kingdom guidelines was used as a reference to assess the appropriateness of control of hypertension. Results: A total of 48 patients had blood pressure>130/80 mm Hg, 42 patients had systolic blood pressure greater than 130 mm Hg, and 31 patients had diastolic pressure greater than 80 mm Hg. All patients with hypertension were on anti-hypertensives with 12 patients being on just 1 type of medication to 3 patients being on 5 different types of medications. 8 patients with hypertension and diabetes were not on angiotensin converting enzyme inhibitors (no contraindications to angiotensin converting enzyme inhibitors). Conclusions: Control of hypertension is poor in patients with chronic renal failure which is contributing to patients requiring dialysis early. Various reasons for inadequate control include less importance to hypertension, fear to over correct — patients may become symptomatic with low blood pressure, disease process itself, probably ineffective antihypertensive which may not work well in chronic renal failure. This study emphasizes to regularly review the anti hypertensive medications and the indications for which they are used. doi:10.1016/j.ijcard.2009.09.312 KI000165 Effects of ACEI and low sodium intake on the renin–angiotensin system in mice with unilateral hydronephrosis Y.L. ZHANG, J.Y. WU, X.C. WANG, X.A. JING Taishan Medical University, China Objective: Administration of ACE inhibitor (ACEI) and low sodium intake (LSI) increase plasma renin concentration. However, it is not
S93
clearly understood how ACEI and LSI alter both renin release and synthesis. The aim of this study was to determine the role of ACEI and LSI in both renin expression and release in hydronephrotic mice. Methods: Balb/C mice (25–30 g) were anesthetized with sodium pentobarbitone (60 mg kg− 1, i.p.) and the left ureter was ligated except sham-operated animals. Four weeks later, the left kidney became hydronephrotic. The mice were divided into four groups (8 animals in each group): Mice in group 1 were controls. Group 2 were left hydronephrotic on a normal diet. Group 3 were given enalapril at a dose of 10 mg kg− 1 day− 1. Group 4 were maintained on a low sodium diet (0.1% NaCl). Seven days later, plasma renin concentration (PRC), renal tissue renin concentration (TRC) and distribution were measured using radioimmunoassay and immunohistochemistry. Results: In mice with the left ureteral ligation, PRC in the left renal vein was lower than in the vein in control mice (P < 0.01). TRC and the renin immunostaining level in the left hydronephrotic kidneys were greater than in the contralateral organs (P < 0.05). In mice treated with enalapril, there was a significant increase in TRC (3-fold) and immunostaining level in the left hydronephrotic kidney. In animals with LSI, TRC and immunostaining were higher in the hydronephrotic kidneys than in the controls (P < 0.01) while PRC did not change. Conclusion: There was no net release from the hydronephrotic kidney. ACEI or LSI significantly stimulated renin levels in the hydronephrotic and normal kidneys but not for release from the ligated kidney. Thus, macula densa appears to be important for renin release in the hydronephrotic mouse. The synthesis and secretion of renin could be disassociated in the kidney with unilateral ureteral ligation. doi:10.1016/j.ijcard.2009.09.313 KI000269 The effect of l-carnitine supplementation on the arterial stiffness in patients on hemodialysis B. CSIKYa,b, F. IGNÁCZa, E. SULYOKc, I. WITTMANNa a Nephrological Center and 2nd Dept. of Medicine, University of Pécs, Hungary b FMC Dialysis Center Pécs, Hungary c Faculty of Health Sciences University of Pécs, Hungary Hypothesis and objectives: The most common cause of morbidity and mortality in patients on chronic hemodialysis is cardiovascular disease. According to data from clinical studies, structural and functional alterations of the large arteries are contributing to the high cardiovascular mortality of these patients. A well accepted way for examining the stiffness of the large arteries is measuring the augmentation index (AIx). l-Carnitine supplementation in hemodialysis patients has beneficial effects on the lipid alterations and is improving cardiac function. There is no data on the effect of lcarnitine supplementation on the arterial stiffness. The aim of the present study was to evaluate the effect of l-carnitine supplementation on the AIx of hemodialysis patients. Patients and methods: Stable chronic hemodialysis patients (n = 22, age = 59 ± 13 years, male/female: 14/8) were supplemented with l-carnitine. 11 patients were normotensive, 11 patients were treated hypertensives. The patients' medical and dialysis treatment was unchanged during the study period. Renal replacement therapy: hemodiafiltration 3 x 4 h weekly using polysulphone membranes. l-Carnitine supplementation: 1,000 mg iv, after each dialysis treatment for 9 weeks. Blood pressure measurements were performed with calibrated automatic devices. AIx was measured by applanation tonometry (SphygmoCor, AtCor Inc) prior to the respective dialysis treatment, before l-carnitine supplementation was started and at the end of the 9th week of supplementation. Results: Predialysis blood pressure measured at the beginning of the carnitine supplementation period and at its end was unchanged (129.3±18.9/76.4±10.9 vs 127.7±12.7/75.2±10.4 mm Hg).
monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and endothelin-1 (ET-1) were determined by real time PCR. The expression of ED-1, transforming growth factor-β (TGF-β), and connective tissue growth factor (CTGF) was determined in the kidney by semiquantitative immunoblotting and immunohistochemistry. In DSH rats, SBP was increased, which was not affected by rosuvastatin treatment. Creatinine clearance was decreased while UAE was increased in DSH rats compared with controls, which were attenuated by rosuvastatin treatment. Glomerulosclerosis and tubulointerstitial fibrosis in DSH rats were attenuated by rosuvastatin treatment. The mRNA expression of MCP-1, ICAM-1, and ET-1 was increased in DSH rats, which was attenuated by rosuvastatin treatment. The expression of ED-1, TGF-β, and CTGF was increased in the kidney of DSH rats, which was counteracted by rosuvastatin treatment. Rosuvastatin is effective in preventing progression of renal injury in DSH rat, the mechanism of which is associated with anti-inflammatory and anti-fibrotic effects. doi:10.1016/j.ijcard.2009.09.311 KI000150 Control of hypertension in chronic renal failure patients VENU MADHAV KONALA, ADARSH BABU, DAVID EADINGTON Hull Royal Infirmary, United Kingdom Objective: Hypertension is one of the important independent risk factors in patients with chronic renal failure. Control of hypertension is essential to slow the cardiovascular risk, stroke and progression of renal disease. Various studies have indicated that hypertension control in patients with chronic kidney disease is poor, even though the awareness is high. This study aimed to look at control of hypertension in patients with chronic kidney disease stages 3 and 4. Design and method: A cross sectional observational study of 100 patients attending pre-dialysis clinic in the year 2007 at a United Kingdom tertiary hospital were randomly selected. We recorded the average blood pressure readings and the cause of hypertension. Number and type of anti-hypertensive medications were also recorded. Renal Association, United Kingdom guidelines was used as a reference to assess the appropriateness of control of hypertension. Results: A total of 48 patients had blood pressure>130/80 mm Hg, 42 patients had systolic blood pressure greater than 130 mm Hg, and 31 patients had diastolic pressure greater than 80 mm Hg. All patients with hypertension were on anti-hypertensives with 12 patients being on just 1 type of medication to 3 patients being on 5 different types of medications. 8 patients with hypertension and diabetes were not on angiotensin converting enzyme inhibitors (no contraindications to angiotensin converting enzyme inhibitors). Conclusions: Control of hypertension is poor in patients with chronic renal failure which is contributing to patients requiring dialysis early. Various reasons for inadequate control include less importance to hypertension, fear to over correct — patients may become symptomatic with low blood pressure, disease process itself, probably ineffective antihypertensive which may not work well in chronic renal failure. This study emphasizes to regularly review the anti hypertensive medications and the indications for which they are used. doi:10.1016/j.ijcard.2009.09.312 KI000165 Effects of ACEI and low sodium intake on the renin–angiotensin system in mice with unilateral hydronephrosis Y.L. ZHANG, J.Y. WU, X.C. WANG, X.A. JING Taishan Medical University, China Objective: Administration of ACE inhibitor (ACEI) and low sodium intake (LSI) increase plasma renin concentration. However, it is not
S93
clearly understood how ACEI and LSI alter both renin release and synthesis. The aim of this study was to determine the role of ACEI and LSI in both renin expression and release in hydronephrotic mice. Methods: Balb/C mice (25–30 g) were anesthetized with sodium pentobarbitone (60 mg kg− 1, i.p.) and the left ureter was ligated except sham-operated animals. Four weeks later, the left kidney became hydronephrotic. The mice were divided into four groups (8 animals in each group): Mice in group 1 were controls. Group 2 were left hydronephrotic on a normal diet. Group 3 were given enalapril at a dose of 10 mg kg− 1 day− 1. Group 4 were maintained on a low sodium diet (0.1% NaCl). Seven days later, plasma renin concentration (PRC), renal tissue renin concentration (TRC) and distribution were measured using radioimmunoassay and immunohistochemistry. Results: In mice with the left ureteral ligation, PRC in the left renal vein was lower than in the vein in control mice (P < 0.01). TRC and the renin immunostaining level in the left hydronephrotic kidneys were greater than in the contralateral organs (P < 0.05). In mice treated with enalapril, there was a significant increase in TRC (3-fold) and immunostaining level in the left hydronephrotic kidney. In animals with LSI, TRC and immunostaining were higher in the hydronephrotic kidneys than in the controls (P < 0.01) while PRC did not change. Conclusion: There was no net release from the hydronephrotic kidney. ACEI or LSI significantly stimulated renin levels in the hydronephrotic and normal kidneys but not for release from the ligated kidney. Thus, macula densa appears to be important for renin release in the hydronephrotic mouse. The synthesis and secretion of renin could be disassociated in the kidney with unilateral ureteral ligation. doi:10.1016/j.ijcard.2009.09.313 KI000269 The effect of l-carnitine supplementation on the arterial stiffness in patients on hemodialysis B. CSIKYa,b, F. IGNÁCZa, E. SULYOKc, I. WITTMANNa a Nephrological Center and 2nd Dept. of Medicine, University of Pécs, Hungary b FMC Dialysis Center Pécs, Hungary c Faculty of Health Sciences University of Pécs, Hungary Hypothesis and objectives: The most common cause of morbidity and mortality in patients on chronic hemodialysis is cardiovascular disease. According to data from clinical studies, structural and functional alterations of the large arteries are contributing to the high cardiovascular mortality of these patients. A well accepted way for examining the stiffness of the large arteries is measuring the augmentation index (AIx). l-Carnitine supplementation in hemodialysis patients has beneficial effects on the lipid alterations and is improving cardiac function. There is no data on the effect of lcarnitine supplementation on the arterial stiffness. The aim of the present study was to evaluate the effect of l-carnitine supplementation on the AIx of hemodialysis patients. Patients and methods: Stable chronic hemodialysis patients (n = 22, age = 59 ± 13 years, male/female: 14/8) were supplemented with l-carnitine. 11 patients were normotensive, 11 patients were treated hypertensives. The patients' medical and dialysis treatment was unchanged during the study period. Renal replacement therapy: hemodiafiltration 3 x 4 h weekly using polysulphone membranes. l-Carnitine supplementation: 1,000 mg iv, after each dialysis treatment for 9 weeks. Blood pressure measurements were performed with calibrated automatic devices. AIx was measured by applanation tonometry (SphygmoCor, AtCor Inc) prior to the respective dialysis treatment, before l-carnitine supplementation was started and at the end of the 9th week of supplementation. Results: Predialysis blood pressure measured at the beginning of the carnitine supplementation period and at its end was unchanged (129.3±18.9/76.4±10.9 vs 127.7±12.7/75.2±10.4 mm Hg).