Increase In Renal Blood Flow Research Articles

Renal angioplasty for treatment of hypertensive patients with fibromuscular dysplasia. No country for old men

Renal angioplasty for treatment of hypertensive patients with fibromuscular dysplasia. No country for old men

PWE-146 Relaxin Is a Renal Vasodilator in Experimental Models of Cirrhosis and A Potential Novel Therapy for Hepatorenal Syndrome in Humans

IntroductionHepatorenal syndrome (HRS) is a feared complication of cirrhosis with a high mortality rate and limited treatment options. The hallmark features of HRS are profound renal vasoconstriction, resulting in a...

Anemia increases the risk of renal cortical and medullary hypoxia during cardiopulmonary bypass

Anemia is an independent predictor of acute kidney injury (AKI) following cardiopulmonary bypass (CPB), possibly due to inadequate renal oxygen delivery. The objective of this study was to investigate the effects of CPB and anemia on tissue oxygen tension (pO2) and blood flow in the renal cortex and medulla. Rats (n=6/group) underwent 1 hr of normothermic cardiopulmonary bypass (CPB), with target hemoglobin concentrations (Hb) of 10 g/dL (CPB) or 6.5 g/dL (anemia-CPB). Renal blood flow (RBF) and tissue PO2 were measured before, during and after 1 hr of CPB. To confirm the observed differences in renal cortical and medullary PO2, HIF-1α (ODD) luciferase mice were exposed to 8% O2 (hypoxia) and HIF-1α dependent luminescence was measured in the renal cortex and medulla (n=5). Renal tissue PO2 values decreased initially and returned towards baseline, however, values at the end of CPB. Anemia-CPB resulted in a significant increase in both renal cortical and medullary blood flow, PO2 remained significantly reduced throughout anemia-CPB. Renal medullary HIF-1α-dependent luminescence confirmed a greater degree of hypoxia in the renal medulla. During CPB, renal O2 delivery was transiently jeopardized, but recovered after 1 hr. Anemia-CPB resulted in a dramatic and sustained reduction in renal cortical and medullary PO2, which suggests an increased risk of renal hypoxic injury with anemia. The clear difference in the degree of hypoxia in the renal cortex and medulla may be useful in understanding the progress of medullary hypoxia during CPB with anemia and the potential development of AKI. Further studies should aim at identifying early markers of medullary hypoxia and potential agents that may decrease the work and O2 consumption in the renal medulla to reduce the risk of hypoxic damage during CPB and anemia.

Saline loading does not change renal medullary blood flow in essential hypertension

In essential hypertension (EH), the natriuresis during saline loading is exaggerated. It was hypothesized that this phenomenon is associated with an increase in renal medullary blood flow. Patients (n=6) with mild, monosymptomatic EH were investigated after an 18‐d drug washout period including 4 d on standardized diet. Regional, renal blood flows were determined before and after saline loading (0.72 mmol/kg/h for 4 h) by Positron Emission Tomography and Computer Tomography (PET/CT) using H215O tracer (Am J Physiol Regul Integr Comp Physiol 299:R1449, 2010). Renal medullary blood flows (ml/(g tissue)/min) were 2.0 ±0.4 and 1.7 ±0.3* before and after saline loading, respectively. During saline loading BP (mmHg) changed from 147.6/86.1 ±6.5/3.1 to 157.1*/92.1† ±4.4/3.3. Renal sodium excretion (μmol/min) increased from 39.2 ±7.0 to 145.6 ±38.5†. It is concluded that the increase in renal sodium excretion during saline loading is not associated with an increase in renal medullary blood flow. *(P = ns) †(P < 0.05)Funded by The Danish Heart Foundation and The University of Southern Denmark.

Angiotensin II Blockade and Renal Protection

Current national guidelines have recommended the use of renin-angiotensin system inhibitors, including angiotensin II type 1 receptor blockers (ARBs), in preference to other antihypertensive agents for treating hypertensive patients with chronic kidney disease. However, the mechanisms underlying the renoprotective effects of ARBs are multiple and complex. Blood pressure reduction by systemic vasodilation with an ARB contributes to its beneficial effects in treating kidney disease. Furthermore, ARB-induced renal vasodilation results in an increase in renal blood flow, leading to improvement of renal ischemia and hypoxia. ARBs are also effective in reducing urinary albumin excretion through a reduction in intraglomerular pressure and the protection of glomerular endothelium and/or podocyte injuries. In addition to blocking angiotensin II-induced renal cell and tissue injuries, ARBs can decrease intrarenal angiotensin II levels by reducing proximal tubular angiotensinogen and production of collecting duct renin, as well as angiotensin II accumulation in the kidney. In this review, we will briefly summarize our current understanding of the pharmacological effects of an ARB in the kidney. We will also discuss the possible mechanisms responsible for the renoprotective effects of ARBs on type 2 diabetic nephropathy.

Resveratrol induces acute endothelium‐dependent renal vasodilation

Resveratrol induces vasorelaxation in endothelium‐intact aortic strips through a nitric oxide (NO) mediated mechanism. We hypothesized resveratrol may act as an acute renal vasodilator through NO and/or prostanoid‐mediated mechanisms. In anesthetized rats, dose response experiments found 5.0 mg/kg resveratrol increased renal blood flow (RBF) by 8% (from 6.98±0.42 to 7.54±0.17 ml/min/gkw n=8 p<0.002), and decreased renal vascular resistance (RVR) by 18% from 15.00±1.65 to 12.32±1.20 ARU (p<0.002). Heart rate (HR) and mean arterial pressure (MAP) remained unchanged. To test NO involvement, we administered 5.0 mg/kg resveratrol, before and after 10 mg/kg b.w. NOS inhibitor L‐NAME. L‐NAME increased MAP 38 mm Hg, decreased RBF by 39%, and doubled RVR. L‐NAME reduced the increase in RBF to resveratrol by 54% (from 0.59±0.05 to 0.27±0.06 ml/min/gkw, n=10 p<0.001). To test the role of endothelium‐derived prostanoids in resveratrol‐induced vasodilation, rats were treated with 10 mg/kg b.w. indomethacin. This treatment did not alter baselines or resveratrol‐induced vasodilation; and L‐NAME reduced resveratrol‐induced vasodilation by 44% from 0.50±0.09 to 0.28±0.06 ml/min/gkw (n=10 p<0.04) as before. We conclude acute intravenous resveratrol acts as an acute renal vasodilator, partially mediated by endothelial NO production but not by vasodilatory prostanoids. (NIH 5P01HL090550–04)

When birth comes early: Effects on nephrogenesis

Preterm birth (birth prior to 37 completed weeks of gestation) may occur at a time when the infant kidney is very immature and nephrogenesis is often ongoing. In autopsied preterm human kidneys and in a baboon model of preterm birth it has been shown that nephrogenesis continues after preterm birth, with a significant increase in the number of glomerular generations and number of nephrons formed within the kidney after birth. Of concern, however, morphologically abnormal glomeruli (with a cystic Bowman's space) are often observed; the abnormal glomeruli are only located in the outer renal cortex, suggesting that it is the recently formed glomeruli (perhaps those formed in the extra-uterine environment) that are affected. The proportion of abnormal glomeruli within the renal cortex differs between infants with some kidneys appearing normal whereas others are severely affected. This suggests that it may be haemodynamic factors and/or factors in the neonatal care of the infant that lead to the glomerular abnormalities. Indeed, the haemodynamic transition at birth where there is a marked increase in systemic blood pressure and renal blood flow are likely to lead to injury of glomerular capillaries, although further studies are required to elucidate this. In order to optimize renal health at the beginning of life in the preterm infant, it is imperative in future studies to gain an understanding of the causes of the glomerular abnormalities in the preterm neonate.

Relaxin is a renal vasodilator in experimental models of cirrhosis and a potential novel therapy for hepatorenal syndrome in man

BackgroundHepatorenal syndrome is a feared complication of cirrhosis, with a high mortality rate and limited treatment options. The hallmarks of the disorder are functional renal failure, normal kidney histological findings, and profound renal vasoconstriction. The hormone relaxin mediates haemodynamic adaptations to pregnancy including increased renal blood flow and glomerular filtration rate (GFR). We hypothesised that relaxin could be used to modulate renal blood flow in cirrhosis. MethodsCirrhosis was induced in male rats by 16 weeks of carbon tetrachloride (intraperitoneally) and decompensated biliary cirrhosis by bile duct ligation. The effect of acute intravenous or extended (72 h) subcutaneous relaxin versus placebo was determined by analysis of systemic haemodynamics, renal blood flow, GFR, and organ histology. The effect of co-treatment with L-NG-nitroarginine methyl ester (L-NAME) was measured in subgroups of relaxin or placebo treated rats. Blood oxygen dependent-MRI (BOLD-MRI) was used to non-invasively detect changes to renal oxygenation. Hepatic and renal expression of RXFP1 (relaxin receptor) was determined by IHC and quantitative PCR (qPCR). A qPCR array was used to quantify changes in renal vasodilator/vasoconstrictor gene expression in response to relaxin. FindingsRXFP1 was detected in glomerular podocytes, renal pericytes, and renal, segmental, and interlobar arteries of cirrhotic rats. In carbon tetrachloride (CCl4) induced cirrhosis, acute intravenous relaxin (4 μg) induced a 50% increase in renal blood flow after 60 min (p<0·01 vs placebo, n=6). BOLD-MRI showed statistically significant (p<0·05) increased tissue oxygenation at the same timepoint in renal cortex and medulla. Extended subcutaneous relaxin increased renal blood flow by 54% in CCl4 (p<0·01 vs placebo, n=8) and 87% in bile duct ligated animals (p<0·05 vs placebo, n=3) and increased GFR by 138% in CCl 4 (p<0·01 vs placebo, n=8) and 70% in bile duct ligated animals (p<0·05 vs placebo, n=3). Mean arterial pressure was unaffected by relaxin. L-NAME (250 mg/L) orally abrogated the effect of relaxin on renal blood flow and GFR. Relative expression of vasoconstrictor genes in kidney was markedly reduced by relaxin treatment. InterpretationRelaxin increases renal blood flow in experimental models of cirrhosis. Crucially, relaxin also improves renal function and oxygenation and does not induce systemic hypotension even in advanced disease. These effects are modulated via augmentation of nitric oxide and downregulation of vasoconstrictors, pivotal in the pathogenesis of hepatorenal syndrome. Relaxin has potential as a novel therapy for hepatorenal syndrome, and further translational studies are warranted. FundingWellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative.

Influence of non-sodium restricted diet with diuretics on plasma rennin, renal blood flow and in patients with cirrhotic ascites

To explore influence of sodium restricted diet and non-sodium restricted diet on plasma rennin (PRA), angiotensin II (All), ALD, renal blood flow (RBF) and subside of ascites in patients with cirrhotic ascites. Eighty cases of hepatitis B with cirrhotic ascites were randomly divided into sodium restricted diet group and non-sodium restricted diet group. 39 cases were in non-sodium restricted diet group, taking sodium chloride 6500-8000 mg daily; 41 cases were in sodium restricted diet group, taking sodium chloride 5000 mg daily. Both groups received diuretics furosemide and spironolactone. Blood sodium, urine sodium, PRA, AII, ALD, RBF ascites subsiding were compared after treatment. In non-sodium restricted diet group, blood sodium and urine sodium increased 10 days after treatment compared with those before treatment, and compared with those of sodium restricted diet group 10 days after treatment, P <0. 01. RBF increased compared with that before treatment, and compared with that of sodium restricted diet group 10 days after treatment, P < 0. 01. Renal damage induced by low blood sodium after treatment was less in non-sodium restricted diet group than that in sodium restricted diet group, P <0. 05. Ascites disappearance upon discharge was more in sodium restricted diet group than that in non-sodium restricted diet group, P <0. 01. Time of ascites disappearance was shorter in non-sodium restricted diet group than that in sodium restricted diet group, P < 0. 01. Compared with sodium restricted diet, while using diuretics of both groups, non-sodium restricted diet can increase level of blood sodium, thus increasing excretion of urine sodium and diuretic effect. It can also decrease levels of PRA, AII and ALD, increase renal blood flow and prevent renal damage induced by low blood sodium and facilitate subsiding of ascites.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

The Natural History of Residual Renal Function in Transplant Donors

After uninephrectomy, GFR in the remaining kidney increases to 60%-70% of the predonation value, largely because of a substantial increase in renal blood flow. Donor kidney function is then generally maintained over many years. Hypertension and proteinuria are common among living donors but do not appear to negatively affect long-term renal function. Loss of reserve capacity regarding renal function in some subgroups after donation, particularly in obese and older donors, raises questions about limitations of the renal adaptive response and suggests caution in generalization of current outcome data to more marginal donors not well represented in older studies.

Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short‐term hypotensive effect

Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP.

Tumor necrosis factor-α receptor type 1, not type 2, mediates its acute responses in the kidney

Acute administration of tumor necrosis factor-α (TNF-α) resulted in decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) but induced diuretic and natriuretic responses in mice. To define the receptor subtypes involved in these renal responses, experiments were conducted to assess the responses to human recombinant TNF-α (0.3 ng·min(-1)·g body wt(-1) iv infusion for 75 min) in gene knockout (KO) mice for TNF-α receptor type 1 (TNFαR1 KO, n = 5) or type 2 (TNFαR2 KO, n = 6), and the results were compared with those obtained in corresponding wild-type [WT (C57BL/6), n = 6] mice. Basal levels of RBF (PAH clearance) and GFR (inulin clearance) were similar in TNFαR1 KO, but were lower in TNFαR2 KO, than WT mice. TNF-α infusion in WT mice decreased RBF and GFR but caused a natriuretic response, as reported previously. In TNFαR1 KO mice, TNF-α infusion failed to cause such vasoconstrictor or natriuretic responses; rather, there was an increase in RBF and a decrease in renal vascular resistance. Similar responses were also observed with infusion of murine recombinant TNF-α in TNFαR1 KO mice (n = 5). However, TNF-α infusion in TNFαR2 KO mice caused changes in renal parameters qualitatively similar to those observed in WT mice. Immunohistochemical analysis in kidney slices from WT mice demonstrated that while both receptor types were generally located in the renal vascular and tubular cells, only TNFαR1 was located in vascular smooth muscle cells. There was an increase in TNFαR1 immunoreactivity in TNFαR2 KO mice, and vice versa, compared with WT mice. Collectively, these functional and immunohistological findings in the present study demonstrate that the activation of TNFαR1, not TNFαR2, is mainly involved in mediating the acute renal vasoconstrictor and natriuretic actions of TNF-α.

Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in rats

Centrally acting leptin induces the activation of the sympathetic nervous system with a pressor effect in normotensive rats. The purpose of the study was to examine central leptin-evoked action in critical haemorrhagic hypotension. In anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with mean arterial pressure (MAP) 20–25mmHg haemodynamic parameters and plasma concentrations of adrenaline and noradrenaline were measured. Leptin given intracerebroventricularly (20μg) evoked long-lasting rises in MAP and heart rate (HR), with a subsequent increase in renal, mesenteric and hindquarters blood flows and a 100% survival at 2h. MAP and peripheral blood flow changes were inhibited by a pre-treatment with α1- and α2-adrenoceptor antagonists prazosin (0.5mg/kg) and yohimbine (1mg/kg), while β-adrenoceptor antagonist propranolol (1mg/kg) blocked leptin-induced HR changes, without influence on MAP, peripheral blood flows and survival. Twenty min after leptin treatment, there were higher plasma concentrations of noradrenaline, but not adrenaline, in comparison with the saline-treated control group. In conclusion, centrally acting leptin induces a long-lasting pressor effect with an improvement in the survival rate in haemorrhage-shocked rats. The effect may be associated with the activation of the sympathetic nervous system.

The Emerging Role of Heme Oxygenase and Its Metabolites in the Regulation of Cardiovascular Function

The Emerging Role of Heme Oxygenase and Its Metabolites in the Regulation of Cardiovascular Function

Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study

IntroductionAcute kidney injury (AKI), which is a major complication after cardiovascular surgery, is associated with significant morbidity and mortality. Diuretic agents are frequently used to improve urine output and to facilitate fluid management in these patients. Mannitol, an osmotic diuretic, is used in the perioperative setting in the belief that it exerts reno-protective properties. In a recent study on uncomplicated postcardiac-surgery patients with normal renal function, mannitol increased glomerular filtration rate (GFR), possibly by a deswelling effect on tubular cells. Furthermore, experimental studies have previously shown that renal ischemia causes an endothelial cell injury and dysfunction followed by endothelial cell edema. We studied the effects of mannitol on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2), and extraction (RO2Ex) in early, ischemic AKI after cardiac surgery.MethodsEleven patients with AKI were studied during propofol sedation and mechanical ventilation 2 to 6 days after complicated cardiac surgery. All patients had severe heart failure treated with one (100%) or two (73%) inotropic agents and intraaortic balloon pump (36%). Systemic hemodynamics were measured with a pulmonary artery catheter. RBF and renal filtration fraction (FF) were measured by the renal vein thermo-dilution technique and by renal extraction of chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), respectively. GFR was calculated as the product of FF and renal plasma flow RBF × (1-hematocrit). RVO2 and RO2Ex were calculated from arterial and renal vein blood samples according to standard formulae. After control measurements, a bolus dose of mannitol, 225 mg/kg, was given, followed by an infusion at a rate of 75 mg/kg/h for two 30-minute periods.ResultsMannitol did not affect cardiac index or cardiac filling pressures. Mannitol increased urine flow by 61% (P < 0.001). This was accompanied by a 12% increase in RBF (P < 0.05) and a 13% decrease in renal vascular resistance (P < 0.05). Mannitol increased the RBF/cardiac output (CO) relation (P = 0.040). Mannitol caused no significant changes in RO2Ext or renal FF.ConclusionsMannitol treatment of postoperative AKI induces a renal vasodilation and redistributes systemic blood flow to the kidneys. Mannitol does not affect filtration fraction or renal oxygenation, suggestive of balanced increases in perfusion/filtration and oxygen demand/supply.

The effect of intravenous insulin infusion on renal blood flow in conscious sheep is partially mediated by nitric oxide but not by prostaglandins1

To test the effect of insulin on renal perfusion and the participation of NO and PG as mediators of this response, renal blood flow (RBF) was measured in sheep (n = 8) implanted with ultrasonic flow probes around renal arteries and with a systemic arterial pressure (SAP, n = 4) telemetry device. Three protocols were performed: 1) RBF and SAP were recorded (0800 to 1800 h) in fed and fasted sheep, with the latter receiving intravenous (i.v.) infusions (0.5 mL/min) of insulin at 2 or 6 mU/(kg·min); 2) fasted sheep received i.v. infusions of either an inhibitor of NO synthesis (N(G)-nitro-L-arginine methyl ester, L-NAME) alone [0.22 mg/(kg·min), 1000 to 1200 h] or L-NAME (1000 to 1200 h) + insulin during the second hour (6 mU/(kg·min), 1100 to 1200 h); and 3) the same protocol was followed as in protocol 2, substituting L-NAME with ketoprofen [0.2 mg/(kg·min)], a cyclooxygenase inhibitor. In all protocols, plasma insulin and glucose were determined. During insulin administration, euglycemia was maintained and hypokalemia was prevented by infusing glucose and KCl solutions. After the onset of meals, a long-lasting 18% increase in RBF and a 48% insulin increase were observed (P < 0.05), without changes in SAP. Low- and high-dose insulin infusions increased RBF by 19 and 40%, respectively (P < 0.05). As after meals, the increases in RBF lasted longer than the insulin increase (P < 0.05). The L-NAME infusion decreased RBF by 15% (P < 0.05); when insulin was added, RBF increased to preinfusion values. Ketoprofen decreased RBF by 9% (P < 0.05); when insulin was added, RBF increased to 13% above preinfusion values (P < 0.05). In no case was a modification in SAP or glucose noted during the RBF changes. In conclusion, insulin infusion mimics the meal-dependent increase in RBF, independent of SAP, and lasts longer than the blood insulin plateau. The RBF increase induced by insulin was only partially prevented by L-NAME. Ketoprofen failed to prevent the insulin-dependent RBF increase. Both facts suggested that complementary vasodilatatory agents accounted for the insulin effect on sheep renal hemodynamics.

Bumetanide

Bumetanide

CYP4A11 T8590C polymorphism, salt-sensitive hypertension, and renal blood flow

A loss-of-function cytosine (C) for thymidine (T) transition at nucleotide 8590 of CYP4A11 has been associated with increased blood pressure in humans. We tested the hypothesis that CYP4A11 T8590C genotype is associated with salt sensitivity in the International Hypertensive Pathotype cohort. CYP4A11 T8590C genotype was associated with hypertension in whites. Among normotensive individuals, CYP4A11 T8590C genotype was associated with mean arterial pressure (MAP) during both high and low salt diets, such that there was no relationship between genotype and salt sensitivity of blood pressure. Among hypertensive individuals, CYP4A11 T8590C genotype did not associate with MAP during high salt intake, whereas MAP decreased with increasing number of C alleles during salt restriction. Consequently, among hypertensive individuals, change in MAP with salt restriction was greatest in individuals homozygous for the C allele (-10.9 ± 9.9, -11.1 ± 12.3, and -18.8 ± 12.0 mmHg in TT, CT, and CC groups, respectively, P = 0.02). In both normotensive and hypertensive individuals, individuals homozygous for the C allele exhibited an attenuated increase in renal blood flow during high salt. CYP4A11 genotype did not affect pressor responses to Angiotensin II in normotensive or hypertensive individuals. The loss-of-function CYP4A11 8590C allele is associated with a diagnosis of hypertension and, in normotensive individuals, with higher blood pressure regardless of salt intake. Among hypertensive individuals, the C allele is associated with salt-sensitive blood pressure. Impaired renal vasodilation during high salt intake may contribute to salt sensitivity. Studies are needed to determine whether CYP4A11 T8590C genotype predicts responses to medications that affect sodium homeostasis in hypertensive individuals.

P23.13: Magnetic resonance fetal lung volumetry for predicting postnatal short‐term outcome in congenital left diaphragmatic hernia

Results: We demonstrated a correlation between PSV of renal artery, PI and vmax of renal vein and gestational age (GA). In addition our results showed that there were no correlation between gestational age and 3-D power Doppler vascular parameters (VI, FI, VFI). Conclusions: Our study indicates that fetal renal blood flow increase with the advancement of gestational age and that bidimensional sonography is more reliable than three-dimensional power Doppler angiography for the study of fetal renal vasculature.