Aso Saeed

High-NaCl intake impairs dynamic autoregulation of renal blood flow in ANG II-infused rats

The aim of this study was to investigate dynamic autoregulation of renal blood flow (RBF) in ANG II-infused rats and the influence of high-NaCl intake. Sprague-Dawley rats received ANG II (250 ng·kg(-1)·min(-1) sc) or saline vehicle (sham) for 14 days after which acute renal clearance experiments were performed during thiobutabarbital anesthesia. Rats (n = 8-10 per group) were either on a normal (NNa; 0.4% NaCl)- or high (HNa; 8% NaCl)-NaCl diet. Separate groups were treated with 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol; 1 M in drinking water). Transfer function analysis from arterial pressure to RBF in the frequency domain was used to examine the myogenic response (MR; 0.06-0.09 Hz) and the tubuloglomerular feedback mechanism (TGF; 0.03-0.06 Hz). MAP was elevated in ANG II-infused rats compared with sham groups (P < 0.05). RBF in ANG II HNa was reduced vs. sham NNa and sham HNa (6.0 ± 0.3 vs. 7.9 ± 0.3 and 9.1 ± 0.3 ml·min(-1)·g kidney wt(-1), P < 0.05). transfer function gain in ANG II HNa was significantly elevated in the frequency range of the MR (1.26 ± 0.50 dB, P < 0.05 vs. all other groups) and in the frequency range of the TGF (-0.02 ± 0.50 dB, P < 0.05 vs. sham NNa and sham HNa). Gain values in the frequency range of the MR and TGF were significantly reduced by tempol in ANG II-infused rats on HNa diet. In summary, the MR and TGF components of RBF autoregulation were impaired in ANG II HNa, and these abnormalities were attenuated by tempol, suggesting a pathogenetic role for superoxide in the impaired RBF autoregulatory response.

Accuracy of colour duplex sonography for the diagnosis of renal artery stenosis.

Objective To examine the diagnostic value of novel velocimetric colour duplex sonography indices in the screening of renal artery stenosis (RAS). Methods We performed a retrospective analysis of all consecutively studied patients at our centre with suspected RAS, and a colour duplex sonography carried out at less than 4 months (mean 34 days) before renal angiography during a 6-year period (2002–2007). A significant RAS was defined as an at least 60% stenosis on angiography or a transstenotic mean arterial pressure gradient of at least 10 mmHg or both. Results In a total of 169 patients, 111 stenotic and 206 nonstenotic kidneys were examined. The sensitivity and specificity for acceleration of blood flow in early systole (ACCmax) were 85 and 75%, respectively, and for the acceleration index (ACCmax/peak systolic velocity, AImax) 83 and 79%, respectively. Corresponding values in patients with estimated glomerular filtration rate of less than 30 ml/min/1.73 m2 were 90 and 73% (for ACCmax) and 74 and 88% (for AImax). In addition, the transstenotic mean arterial pressure gradient showed a significant, though weak, negative correlation to ACCmax (r = −0.26, P = 0.02) and AImax (r = −0.29, P = 0.01) in stenotic kidneys. Conclusion ACCmax and AImax provide similar, good diagnostic accuracy in the detection of a haemodynamically significant RAS, even in patients with markedly reduced glomerular filtration rate. Presumably, the lack of superiority of the novel index AImax could be explained by a highly homogenous methodological approach in the present single-centre study.

Oxidative Stress and Endothelin-1 in Atherosclerotic Renal Artery Stenosis and Effects of Renal Angioplasty

Aims: To examine biomarkers of oxidative stress (oxs), and endothelin (ET)-1, in hypertensive patients with atherosclerotic renal artery stenosis (ARAS) and to evaluate the effect of percutaneous transluminal renal angioplasty (PTRA). Methods: Baseline measurements were made immediately before renal angiography in patients with suspected ARAS (significant ARAS, n = 83, and non-RAS, n = 59) and in 20 healthy, matched controls. In patients with ARAS, analyses were repeated 4 weeks after PTRA. All patients were treated with statins and acetylsalicylic acid throughout. Results: At baseline there were no significant differences between groups in biomarkers of oxs, whereas high-sensitivity C-reactive protein and blood leukocytes were significantly elevated in group ARAS versus both healthy controls and group non-RAS. Plasma levels of ET-1 and uric acid were significantly increased in group ARAS versus healthy controls prior to angiography and were significantly reduced compared to baseline 4 weeks after PTRA. PTRA had no significant effects on biomarkers of oxs, inflammation or serum creatinine concentrations. Conclusions: ARAS patients on treatment with antihypertensive agents, acetylsalicylic acid and statins showed elevated inflammatory indices but no increase in oxs. PTRA had no significant effects on inflammatory indices 4 weeks after intervention but reduced plasma ET-1 and uric acid.

High-NaCl diet impairs dynamic renal blood flow autoregulation in rats with adenine-induced chronic renal failure

This study examined the effects of 2 wk of high-NaCl diet on kidney function and dynamic renal blood flow autoregulation (RBFA) in rats with adenine-induced chronic renal failure (ACRF). Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls). After 10 wk, rats were randomized to either remain on the same diet (0.6% NaCl) or to be switched to high 4% NaCl chow. Two weeks after randomization, renal clearance experiments were performed under isoflurane anesthesia and dynamic RBFA, baroreflex sensitivity (BRS), systolic arterial pressure variability (SAPV), and heart rate variability were assessed by spectral analytical techniques. Rats with ACRF showed marked reductions in glomerular filtration rate and renal blood flow (RBF), whereas mean arterial pressure and SAPV were significantly elevated. In addition, spontaneous BRS was reduced by ∼50% in ACRF animals. High-NaCl diet significantly increased transfer function fractional gain values between arterial pressure and RBF in the frequency range of the myogenic response (0.06-0.09 Hz) only in ACRF animals (0.3 ± 4.0 vs. -4.4 ± 3.8 dB; P < 0.05). Similarly, a high-NaCl diet significantly increased SAPV in the low-frequency range only in ACRF animals. To conclude, a 2-wk period of a high-NaCl diet in ACRF rats significantly impaired dynamic RBFA in the frequency range of the myogenic response and increased SAPV in the low-frequency range. These abnormalities may increase the susceptibility to hypertensive end-organ injury and progressive renal failure by facilitating pressure transmission to the microvasculature.

Effects of endothelin receptor antagonists on renal hemodynamics in angiotensin II-infused rats on high NaCl intake.

Aim: The aim was to investigate effects of selective endothelin (ET) receptor antagonists on renal hemodynamics and dynamic renal blood flow autoregulation (RBFA) in angiotensin II (Ang II)-infused rats on a high NaCl intake. Methods: Sprague-Dawley rats received Ang II (250 ng/kg/min, s.c.) and an 8 % NaCl diet for 14 days after which renal clearance experiments were performed. After baseline measurements animals were administered either: (a) saline vehicle; (b) ETA receptor antagonist BQ-123 (30 nmol/kg/min); (c) ETB receptor antagonist BQ-788 (30 nmol/kg/min); or (d) BQ-123 + BQ-788, for six consecutive 20-minute clearance periods. Results: BQ-123 reduced arterial pressure (AP) and selectively increased outer medullary perfusion versus vehicle (p<0.05). These effects were attenuated or abolished by combined BQ-123 and BQ-788. BQ-788 reduced renal blood flow and increased renovascular resistance (p<0.05). Ang II-infused rats on high NaCl intake showed abnormalities in dynamic RBFA characterized by an impaired myogenic response that were not significantly affected by ET receptor antagonists. Conclusion: In hypertensive Ang II-infused rats on a high-NaCl intake selective ETA antagonism with BQ-123 reduced AP and specifically increased OM perfusion and these effects were dependent on intact ETB receptor stimulation. Furthermore, ET receptor antagonists did not attenuate abnormalities in dynamic RBFA.

Brain Natriuretic Peptides in Atherosclerotic Renal Artery Stenosis and Effects of Renal Angioplasty

Background: We hypothesized that plasma levels of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) would be elevated, and adiponectin concentrations reduced, in patients with atherosclerotic renal artery stenosis (ARAS) and that BNPs might be used to identify patients who would benefit from percutaneous transluminal renal angioplasty (PTRA). Methods: Data were collected before renal angiography in 91 patients with hypertension and suspected ARAS (significant ARAS; n=47, and non-RAS; n=44) and in 20 healthy controls (C). In ARAS patients analyses were repeated four weeks after PTRA. Results: Ambulatory systolic blood pressure (ASBP) was significantly elevated in the ARAS group vs. both C and non-RAS groups. Baseline plasma BNP and NT-proBNP levels were significantly elevated, and adiponectin concentrations reduced, in the ARAS group vs. C but not vs. the non-RAS group. One month after PTRA, ASBP was reduced vs. baseline (149±16 to 139±15 mm p<0.01). Brain natriuretic peptides were not significantly affected by PTRA. Conclusions: Patients with ARAS showed elevated of BNP and NT-proBNP concentrations, and reduced levels of adiponectin, compared to healthy controls but not vs. hypertensive individuals without RAS. Our data do no support the use of BNP analyses in the identification of ARAS patients who will have a beneficial blood pressure response to PTRA.

Lipoprotein abnormalities in patients with atherosclerotic renovascular disease.

Background: Patients with atherosclerotic renovascular disease (ARVD) have a high risk of cardiovascular death. The primary aim was to characterize abnormalities in apolipoprotein (Apo)-defined lipoprotein (Lp) subclasses in patients with ARVD. Methods: Baseline measurements were performed on 42 patients with ARVD 4 weeks after renal angioplasty (PTRA). All patients were on statin treatment. Twenty age-matched healthy subjects without medications served as controls. Subsequently, patients were randomized to treatment with either candesartan (n = 21), or antihypertensive treatment without inhibitors of the renin-angiotensin-aldosterone system (n = 21) and followed for 11 months. Results: At baseline, ApoC-III (12.7 ± 4.6 vs. 8.8 ± 2.6 (SD) mg/dl, p < 0.05), LpB:C:E (13.3 ± 5.4 vs. 8.4 ± 4.3 mg/dl, p < 0.05), and the sum of ApoC-III-containing lipoproteins, i.e. LpB:C + LpB:C:E + LpA-II:B:C:D:E (46 ± 15 vs. 37 ± 8 mg/dl, p < 0.05), were significantly elevated in ARVD patients versus healthy controls. Multiple regression analyses showed that only plasma renin activity was independently associated with ApoC-III levels at baseline (p < 0.05, r = 0.74). Treatment with candesartan did not correct abnormalities. Conclusions: Patients with ARVD treated with statins have an atherogenic lipoprotein profile characterized by elevated levels of ApoC-III-containing, triglyceride-rich lipoproteins that could accelerate atherosclerotic disease.

Split renal function in patients with unilateral atherosclerotic renal artery stenosis—effect of renal angioplasty

Abstract Objective To evaluate the effect of percutaneous transluminal renal angioplasty (PTRA) on split renal function (SRF) in patients with unilateral atherosclerotic renal artery stenosis (ARAS). Methods We performed a retrospective analysis of all consecutively examined patients at our centre with significant ARAS undergoing PTRA during 2002–07. A significant ARAS was defined as a lesion with a trans-stenotic mean arterial pressure gradient of at least 10 mmHg or a diameter stenosis >50% on angiography. Ambulatory (24 h) systolic and diastolic blood pressure (ASBP and ADBP, respectively) and calculated SRF using 99mTc-DTPA renal scintigraphy were evaluated before (baseline) and 4 weeks after PTRA. Results ASBP and ADBP were significantly lower 4 weeks after PTRA compared with baseline levels. Although total estimated glomerular filtration rate (eGFR; four-variable Modification of Diet in Renal Disease equation) had not changed by PTRA, analysis of SRF showed significantly increased eGFR in stenotic kidneys and a comparable reduction in eGFR in non-stenotic kidneys 4 weeks after PTRA. Conclusions In patients with unilateral ARAS, PTRA significantly improved eGFR in stenotic kidneys and decreased filtration in contralateral, non-stenotic kidneys. These potentially beneficial effects may not be apparent when total renal function remains stable. The clinical significance of these findings needs to be evaluated further.

High-NaCl Diet Aggravates Cardiac Injury in Rats with Adenine-Induced Chronic Renal Failure and Increases Serum Troponin T Levels

Aims: To examine the effects of 2 weeks of high-NaCl diet on left ventricular (LV) morphology and serum levels of cardiac troponin T (cTnT) in rats with adenine-induced chronic renal failure (ACRF). Methods: Male Sprague-Dawley rats either received chow containing adenine or were pair-fed an identical diet without adenine [controls (C)]. Approximately 10 weeks after the beginning of the study, the rats were randomized to either remain on a normal NaCl diet (NNa; 0.6%) or to be switched to high-NaCl chow (HNa; 4%) for 2 weeks, after which acute experiments were performed. Results: Rats with ACRF showed statistically significant increases (p < 0.001) in arterial pressure (AP), LV weight and fibrosis, and serum cTnT levels compared to controls. Two weeks of high-NaCl intake augmented the increases in AP, LV weight and fibrosis, and serum cTnT concentrations only in ACRF rats (p < 0.05 for group × NaCl intake interaction). Compared to group C-NNa, cTnT levels were elevated approximately 6-fold in group ACRF-NNa and 24-fold in group ACRF-HNa. Focal LV injury with cardiomyocyte necrosis, scarring, and fibrinoid necrosis of small arteries were only detected in group ACRF-HNa. There was a strong correlation between the degree of LV fibrosis and serum cTnT levels in ACRF rats (r = 0.81, p < 0.01). Conclusion: Two weeks of high-NaCl diet in rats with ACRF produces LV injury and aggravates increases in serum cTnT levels, presumably by causing hypertension-induced small artery lesions leading to myocardial ischemia. This model may be suitable for studying pathophysiological mechanisms in chronic renicardiac syndromes.

Adenine-Induced Chronic Renal Failure in Rats: A Model of Chronic Renocardiac Syndrome with Left Ventricular Diastolic Dysfunction but Preserved Ejection Fraction

Background/Aims: Cardiovascular disease is the major cause of death in patients with chronic kidney disease (CKD). Rats with adenine-induced chronic renal failure (ACRF) develop severe renal insufficiency and metabolic abnormalities that closely resemble those in patients with uremia. The aim of the present study was to determine left ventricular (LV) morphology and function in rats with ACRF. Methods: Male Sprague-Dawley rats received either chow containing adenine or were pair-fed an identical diet without adenine (controls, C). After 9-13 weeks animals were anesthetized with isoflurane and cardiac function was assessed both by echocardiography and by LV catheterization. Results: Rats with ACRF showed increases in serum creatinine (323±107 vs. 33±5 µM, P< 0.05), mean arterial pressure (115±6 vs. 106±7 mmHg, P< 0.05) and LV weight (3.4±0.3 vs. 2.5±0.2 mg/kg, P< 0.05) vs. controls. Rats with ACRF had reduced early diastolic tissue Doppler velocities in the LV, enlarged left atrial diameter (4.8±0.8 vs. 3.5±0.4 mm, P< 0.05) and elevated LV end-diastolic pressure (15±5 vs. 8±1 mmHg, P< 0.01). Cardiac output was increased in ACRF rats (211±66 vs. 149±24 ml/min, P< 0.05) and systolic function preserved. In the LV of ACRF rats there were statistically significant (P< 0.05) increases in cardiomyocyte diameter, proliferation and apoptosis, while there was no difference between groups in fibrosis. Conclusion: Rats with ACRF develop LV hypertrophy and diastolic dysfunction while systolic performance was preserved. There was an increased hypertrophy and apoptosis of cardiomyocytes in the LV of ACRF rats. The cardiac abnormalities in ACRF rats resemble those in patients with CKD in which heart failure with preserved ejection fraction is common. Hence, this experimental model is well suited for studying pathophysiological mechanisms in chronic renocardiac syndromes.