Background. The aim of the study was to investigate the antihypertensive effects of angiotensin I... more Background. The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. Methods. Six-month-old female SHR were randomly selected in six groups. Two control groups (SH 6 , SH 12) received vehicle. Groups ADR 6 , ADR+LOS 6 and ADR 12 , and ADR+LOS 12 received ADR (2 mg/kg/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS 6 received losartan (10 mg/kg/b.w./day by gavages) for 6 weeks and group ADR+LOS 12 for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. Results. Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. Conclusion. Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to endstage renal disease in SHR.
Objective: Acute renal failure (ARF) and hypertension as a comorbid disorders can be found freque... more Objective: Acute renal failure (ARF) and hypertension as a comorbid disorders can be found frequently in intensive care unit patients. The aim of our study was to investigate the antihypertensive effects of 4-Hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl (tempol), synthetic SOD mimetic, on regional haemodynamics in the course of ARF in hypertension. Design and Method: Experiment was performed in anesthetized, six-month-old male spontaneously hypertensive rats (SHR). The right kidney was removed and ARF was induced by clamping the left renal artery for 40 minutes. SHR were divided in 3 experimental groups: sham operated group (SHAM; n = 7); ARF group (ARF; n = 9); and ARF group with tempol treatment (40 mg/kg/h) (ARF+TEM; n = 8). Tempol was given by infusion during the period of three hours after reperfusion. Mean arterial pressure (MAP), carotid blood flow (CBF) and renal blood flow (RBF) were measured and carotid vascular resistance (CVR) and renal vascular resistance (RVR) was calculated 24 h after reperfusion. Results: Figure 1. No caption available. Conclusion: Our results indicate that in hypertension free oxygen species contribute to renal vasoconstiction, one of the major pathophysiological mechanism of postischemic ARF.
Many studies in hypertensive humans and animals have shown that increased blood viscosity is in d... more Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR). Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite-lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.
Background. The aim of the study was to investigate the antihypertensive effects of angiotensin I... more Background. The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. Methods. Six-month-old female SHR were randomly selected in six groups. Two control groups (SH 6 , SH 12) received vehicle. Groups ADR 6 , ADR+LOS 6 and ADR 12 , and ADR+LOS 12 received ADR (2 mg/kg/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS 6 received losartan (10 mg/kg/b.w./day by gavages) for 6 weeks and group ADR+LOS 12 for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. Results. Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. Conclusion. Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to endstage renal disease in SHR.
Objective: Acute renal failure (ARF) and hypertension as a comorbid disorders can be found freque... more Objective: Acute renal failure (ARF) and hypertension as a comorbid disorders can be found frequently in intensive care unit patients. The aim of our study was to investigate the antihypertensive effects of 4-Hydroxy-2, 2, 6, 6-tetramethylpiperidine-N-oxyl (tempol), synthetic SOD mimetic, on regional haemodynamics in the course of ARF in hypertension. Design and Method: Experiment was performed in anesthetized, six-month-old male spontaneously hypertensive rats (SHR). The right kidney was removed and ARF was induced by clamping the left renal artery for 40 minutes. SHR were divided in 3 experimental groups: sham operated group (SHAM; n = 7); ARF group (ARF; n = 9); and ARF group with tempol treatment (40 mg/kg/h) (ARF+TEM; n = 8). Tempol was given by infusion during the period of three hours after reperfusion. Mean arterial pressure (MAP), carotid blood flow (CBF) and renal blood flow (RBF) were measured and carotid vascular resistance (CVR) and renal vascular resistance (RVR) was calculated 24 h after reperfusion. Results: Figure 1. No caption available. Conclusion: Our results indicate that in hypertension free oxygen species contribute to renal vasoconstiction, one of the major pathophysiological mechanism of postischemic ARF.
Many studies in hypertensive humans and animals have shown that increased blood viscosity is in d... more Many studies in hypertensive humans and animals have shown that increased blood viscosity is in direct relation with essential hypertension. The aim of our studies was to investigate the effects of chronic hematocrit value changes on arterial blood pressure and kidney function in genetically induced hypertension. To this end, we studied the effects of several interventions, designed to increase/decrease hematocrit, on hemodynamic parameters, vascular reactivity, glomerular filtration and renal function curve in spontaneously hypertensive rats (SHR). Results of our study show that chronic hematocrit value elevation increases blood pressure and peripheral vascular resistance in SHR. On the other hand, chronic hematocrit lowering elucidates blood pressure and peripheral vascular resistance decrease followed by cardiac output rising. Both hematocrit value changes significantly reduce vasodilatory vascular response. Hematocrit lowering induces acute renal failure. Sodium excretion is shifted to higher blood pressure values in high hematocrit value animals and opposite-lower blood pressure values in low hematocrit value animals. Repeated transfusions develop salt sensitive malignant hypertension in SHR. Further studies are necessary to evaluate the degree of kidney damage after chronic hematocrit value changes in SHR.
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