To study arterial stiffness in CKD by AASI compared to Augmentation Index (AIx) and aortic pulse wave velocity (aPWV). To study the intrapatient reproducibility of AASI in CKD. Patients were studied 2 days within 2 weeks. Double applanation tonometry recordings of the radial pressure wave form and aPWV and 24-h ambulatory blood pressure measurements were done. AASI was calculated as 1 minus the regression slope of diastolic over systolic blood pressure. CKD stage was determined by estimated glomerular filtration rate. Spearman’s correlation coefficient (SCC) was used for evaluating correlations. Day-to-day reproducibility was evaluated by the intra-class correlation coefficient (ICC). 68 patients (M50:F18), median age 63 years (range 30-79), with CKD stage 2 (n = 17), stage 3 (n = 22), stage 4 (n = 20) and stage 5 (n = 9) were studied. Mean(±SD) AASI was 0.44±0.15, mean AIx was 28.2

Objective. Applanation tonometry for pulse-wave analysis (PWA) and determination of pulse-wave velocity (PWV) is a non-invasive method for assessment of the central aortic pressure waveform and indices of arterial stiffness. The objective of this study was to examine the influence of eating and smoking on PWA and PWV measurements in order to establish standard examination conditions. Furthermore, intra- and interobserver reproducibility and the effects of varying the site of measurements were observed. Material and methods. Duplicate measurements of the radial pressure waveform and of the brachial and aortic PWV on the right and left side of the body were recorded in 23 healthy subjects by two trained observers. Measurements were performed in the fasting state and 3 h after a high-calorie meal, and before and 1 h after smoking a cigarette. Results. Intake of a high-calorie meal as well as smoking caused significant changes in both PWA and PWV parameters and an inter-arm difference was observed. Intra- and interobserver reproducibility was good. Conclusions. Pulse-wave measurements by applanation tonometry should be undertaken in the same arm during fasting and smoking abstinence.

Nitric oxide (NO) influences tubular fluid and electrolyte transport, and hence possibly also fluid accumulation in renal cysts. The expression and activity of intrarenal constitutive NO synthase (cNOS) [neuronal NOS, nNOS and endothelial NOS, eNOS] and inducible NOS (iNOS) and plasma nitrite/nitrate (PNOx) concentration were assessed in homozygous Han:SPRD polycystic kidney disease (PKD) rats (cy/cy), heterozygous Han:SPRD PKD rats (cy/+), homozygous normal Han:SPRD littermates (+/+) and Sprague Dawley rats (sd). The results showed: 1) nNOS expression was decreased in proximal tubules and thick ascending limbs of the loop of Henle in cy/cy and cy/+ rats compared to +/+ and sd rats (p<0.05). nNOS was weakly expressed in the epithelium of small cysts and unexpressed in epithelium of large cysts. 2) iNOS expression was increased in proximal tubular epithelial cells in cy/+ rats compared to +/+ rats and sd rats (p<0.01). iNOS expression in cyst epithelium was decreased in cy/+ rats (p<0.05) and absent in cy/cy rats. 3) eNOS expression was similar in the endothelium of intrarenal arteries in all groups. 4) The activity of renal cNOS was decreased in cy/cy and cy/+ rats; the activity of iNOS was decreased only in cy/cy rats, with no significant difference among the other three groups. 5) PNOx concentration was higher in cy/cy rats than in the other three groups, and correlated positively with plasma creatinine and urea. In conclusion, NOS expression and activity decreased as cysts developed, suggesting that NO downregulation is involved in the pathogenesis of PKD.

Elung-Jensen, T; Heisterberg, J; Kamper, A-L; Sonne, J; Strandgaard, S Author Information

The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid 133Xe injection method, whereas blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 h. Five groups of animals were studied: 1) nephrectomized dialyzed rats, 2) nephrectomized dialyzed rats given a single intravenous dose of the angiotensin-converting enzyme inhibitor captopril (10 mg/kg), 3) sham nephrectomized and dialyzed rats, 4) rats receiving drugs as dialyzed rats but no surgery, and 5) rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared with controls. Nephrectomy, captopril, sham operation, or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53 +/- 4 mmHg) and sham-operated (58 +/- 4 mmHg) rats compared with diet control rats (78 +/- 3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35 +/- 2 mmHg). Thus removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls.

AIMSIn chronic renal failure, the clearance of most ACE inhibitors including enalapril is reduced. Hence, with conventional dosage, plasma enalaprilat may be markedly elevated. It is unclear whether this excess of drug exposure affords an improved control of blood pressure. The aim of the present study was to evaluate short-term blood pressure response to two different plasma levels of enalaprilat.METHODSAs part of an open, randomized, controlled trial of the effect of high and low dosage of enalapril on the progression of renal failure, short-term blood pressure response was evaluated. Data were analysed in all patients completing 3 months of follow-up. The patients were allocated to two trough plasma concentrations of enalaprilat, either above 50 ng ml(-1) (high) (n = 17) or below 10 ng ml(-1) (low) (n = 18), and the daily dose of enalapril titrated accordingly.RESULTSMedian (range) glomerular filtration rate (GFR) at baseline was 18 (7.9) in the high enalaprilat concentration group and 17 (7.3) ml min(-1) 1.73 m(2) in the low concentration group (NS). Nine patients in each group were on treatment with enalapril at baseline with a median daily dose of 5 mg in both the high (5-10) and low (2.5-20) concentration group. At 3 months' follow-up, the dose was 10 (2.5-30) and 1.9 (1.25-5) mg (P < 0.0001), respectively. After 3 months median trough concentrations of enalaprilat were 82.5 (22-244) ng ml(-1) and 9.1 (2.5-74.8) ng ml(-1) (P < 0.002). At baseline the median systolic blood pressures in the two groups were 140 (110-200) and 133 (110-165), in the high and low enalaprilat concentration groups, respectively, and after 3 months they were 135 (105-170) and 130 (105-170) mmHg (NS). Median diastolic blood pressure was 80 mmHg in each group both at baseline (65-100) and at follow-up (60-95) (NS). There was no difference between the groups in concomitant antihypertensive treatment (number of patients treated, mean daily dose) during the observation period. Proteinuria remained stable during the study period in both groups; patients in the high concentration group had higher plasma potassium concentrations at day 90 and patients in the low group experienced a slight increase in GFR.CONCLUSIONSIn moderate to severe chronic renal insufficiency the same degree of blood pressure control was achieved on low as well as moderate daily doses of enalapril. This was irrespective of concomitant antihypertensive treatment.

BACKGROUND:Patients with autosomal-dominant polycystic kidney disease (ADPKD) have defective endothelium-dependent relaxation (EDR). We investigated the relationship between endothelial dysfunction and nitric oxide generation in hypertension and chronic renal insufficiency (CRI) in ADPKD.METHODS:We contrasted acetylcholine (ACh)-induced EDR, 3-morphollinosydnonimine (SIN-1)-induced endothelium-independent relaxation (EIDR) and constitutive nitric oxide synthase (cNOS) activity in subcutaneous resistance vessels and plasma levels and excretion of NO2-/NO3- (NOX) in normal, control (N = 10) patients with ADPKD or essential hypertension.RESULTS:EDR was decreased significantly in normotensive ADPKD (N = 9), but more severely in hypertensive ADPKD (N = 6), or those with CRI (N = 5) and in essential hypertension (N = 9). The increases in EDR with l-arginine and decreases with LG-nitro-l-arginine methyl ester (L-NAME) were lost in all groups of patients with ADPKD and in essential hypertension except for a modest effect of L-NAME in normotensive ADPKD. EIDR was unimpaired throughout. Vascular cNOS activity and renal NOX excretion were reduced profoundly in patients with all categories of ADPKD and especially in those with hypertension.CONCLUSION:EDR in resistance vessels from patients with ADPKD is impaired even in the absence of hypertension or CRI, but becomes more marked as hypertension develops. Patients with ADPKD have defective nitric oxide generation from diminished cNOS activity. Endothelial dysfunction and impaired cNOS activity in ADPKD may predispose to hypertension whose occurrence is accompanied by a further sharp deterioration in EDR.

Objective The aim of the present study was to develop a rat model for in vivo studies of the local effects of the renin-angiotensin system (RAS) following elimination of circulating renin. Methods Sprague Dawley rats were bilaterally nephrectomised and had a peritoneal dialysis catheter implanted. The rats were maintained on dialysis continuously for 48 hours, using Dianeal PD4 3.86% glucose dialysis solution. The peritoneal catheter and an automated system for dialysate exchange were made in our laboratory. A sham nephrectomised control group of rats was also dialysed. Results Nephrectomised and sham-operated rats remained active and in good general condition during peritoneal dialysis. At 48 hours, in nephrectomised, dialysed rats, peritoneal urea clearance was 4.14±0.52 ml/hour, plasma urea was 40.0±7.7 mmol/L, plasma creatinine was 0.423±0.070 mmol/L and plasma renin was below the limit of detection. Conclusions In conclusion, it was possible to sustain bilaterally-nephrectomised rats on continuous peritoneal dialysis for 48 hours, pending elimination of renin from the circulation. The nephrectomised dialysed rat model should be useful for investigation of the physiological effects of the circulating versus the local RAS.