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Simple Summary: Organs as well as cancer require a supply of nutrients and oxygen and removal of waste products. These tasks are carried out by the vascular system. Knowledge of the vascular properties in organs and tumors is key for understanding normal and abnormal function. For cancer, vascular function is also highly relevant to understand response to treatment, metastasis, and tumor progression. In this study, we use various techniques to characterize the vascular tree and flow in kidneys with kidney cancer. We connected kidneys to a perfusion system and used barium sulphate contrast to visualize the vascular architecture contact microangiography. Immunohistochemistry was used to visualize the vessels in relation to perfusion. The vascular resistance was measured using the radioactive microspheres and in cases that were feasible, we used micro-CT to characterize the vascular tree. This work aims to suggest the use of these techniques for any organ or tumor available for ex vivo perfusion. This work describes a comprehensive study of the vascular tree and perfusion characteristics of normal kidney and renal cell carcinoma. Methods: Nephrectomy specimens were perfused ex-vivo, and the regional blood flow was determined by infusion of radioactive microspheres. The vascular architecture was characterized by micronized barium sulphate infusion. Kidneys were subsequently sagitally sectioned, and autoradiograms were obtained to show the perfusate flow in relation to adjacent contact X-ray angiograms. Vascular resistance in defined tissue compartments was quantified, and finally, the tumor vasculature was 3D reconstructed via the micro-CT technique. Results show that the vascular tree of the kidney could be distinctly defined, and autoradiograms disclosed a high cortical flow. The peripheral resistance unit of the whole perfused specimen was 0.78 ± 0.40 (n = 26), while that of the renal cortex was 0.17 ± 0.07 (n = 15 with 114 samples). Micro-CT images from both cortex and medulla defined the vascular architecture. Angiograms from the renal tumors demonstrated a significant vascular heterogeneity within and between different tumors. A dense and irregular capillary network characterized peripheral tumor areas, whereas central parts of the tumors were less vascularized. Despite the dense capillarity, low perfusion through vessels with a diameter below 15 µm was seen on the autoradiograms. We conclude that micronized barium sulphate infusion may be used to demonstrate the vascular architecture in a complex organ. The vascular resistance was low, with little variation in the cortex of the normal kidney. Tumor tissue showed a considerable vascular structural heterogeneity with low perfusion through the peripheral nutritive capillaries and very poor perfusion of the central tumor, indicating intratumoral pressure exceeding the perfusion pressure. The merits and shortcomings of the various techniques used are discussed. [ABSTRACT FROM AUTHOR]

Objective: To present two-dimensional/three-dimensional (2D/3D) SlowflowHD features of the fetal duplex kidney. Case description: Two fetal unilateral duplex kidneys at 30 and 32+3 weeks were identified between February 2023 and January 2024. Lengths of both kidneys were >95th percentile of the reference ranges of the normal fetal kidney. Two separate noncommunicating renal pelvises (RP) were evident by 2D sonography and HDlive silhouette. 2D/3D SlowflowHD clearly showed perihilar renal arterial branching and characteristic bridge vessels between the upper renal moiety and lower kidney. Conclusion: SlowflowHD may provide novel and unique vascular information on fetal renal anomalies such as the duplex kidney. [ABSTRACT FROM AUTHOR]

Introduction: Renal ectopia also known as ectopic kidney is an embryological renal abnormality characterized by abnormal anatomical location of one or both kidneys. Kidneys can vary in number, shape, size, position, rotation and vascularization. These variations are of immense importance due to their susceptibility to trauma, infection and iatrogenic injury.We reported the first case of bilateral renal ectopia associated with a bilateral accessory renal artery, a retro-aortic left renal vein and a variation of the renal pelvis. Case report: During a routine dissection of a male cadaver, showing no trace of trauma or surgical scar in the abdomen, we observed a rare case of bilateral renal ectopia and bilateral accessory renal artery. The left renal vein was retro-aortic and anastomosed with the left common iliac vein. We also observed the right renal vein drained the testicular vein, the fusion of the major calyxes (formation of the renal pelvis) outside the right kidney. These observations are of paramount importance to interventional radiologists, nephrologists and vascular surgeons. Conclusion: Renal vasculature variations are common in the population and are important not only for surgeons, but for radiologists. Therefore, a good knowledge of the multiple variations of renal vessels and renal ectopia is important for urologists and radiologists when performing kidney surgeries in kidney donors and transplants, in the end to avoid otherwise to reduce the rate of haemorrhage by accidental lesions of the accessory arteries during surgeries involving the kidneys in particular.

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) induces cardiac and cerebral microvascular dysfunction via increased glycation, oxidative stress and endothelial activation. Liraglutide, a glucagon‐like peptide‐1 analogue, inhibited NOX2 and adhesion molecules in isolated endothelial cells. Here, we have studied how Liraglutide affects advanced glycation, NOX expression and inflammation of the cardiac, cerebral and renal microvasculature in diabetic rats. Methods: DM was induced in Sprague–Dawley rats (n = 15) via intraperitoneal streptozotocin (STZ) injection (60 mg/kg bodyweight). Ten control rats remained nondiabetic. From day 9 post‐STZ injection, Liraglutide (200 μg/kg bodyweight; n = 7) or vehicle (n = 8) was injected subcutaneously daily until termination on day 29. The advanced glycation endproduct N‐ε‐(carboxymethyl)lysine (CML), NOX2, NOX4, ICAM‐1 and VCAM‐1 were subsequently immunohistochemically analysed and quantified to compare Liraglutide treatment with placebo. Results: In the heart, Liraglutide treatment significantly reduced the DM‐increased scores/cm2 for CML in both ventricles (from 253 ± 53 to 72 ± 12; p =.003) and atria (343 ± 29 to 122 ± 8; p =.0001) and for NOX2, ICAM‐1 and VCAM‐1, but not for NOX4. Also in the cerebrum and cerebellum of the brain, Liraglutide significantly reduced the scores/cm2 for CML (to 60 ± 7 (p =.0005) and 47 ± 13 (p =.02), respectively), and for NOX2 and NOX4. In the kidney, the DM‐induced expression of ICAM‐1 and VCAM‐1 was decreased in the blood vessels and glomeruli by Liraglutide treatment. Liraglutide did not affect blood glucose levels or bodyweight. Conclusions: Our study implies that Liraglutide protects the cardiac, cerebral and renal microvasculature against diabetes‐induced dysfunction, independent of lowering blood glucose in a type 1 diabetes rat model. [ABSTRACT FROM AUTHOR]

Members of the transient receptor potential (TRP) channels that are expressed in the kidney have gained prominence in recent years following discoveries of their role in maintaining the integrity of the filtration barrier, regulating tubular reabsorption of Ca2+ and Mg2+, and sensing osmotic stimuli. Furthermore, evidence has linked mutations in TRP channels to kidney disease pathophysiological mechanisms, including focal segmental glomerulosclerosis, disturbances in Mg2+ homeostasis, and polycystic kidney disease. Several subtypes of TRP channels are expressed in the renal vasculature, from preglomerular arteries and arterioles to the descending vasa recta. Although investigations on the physiological and pathological significance of renal vascular TRP channels are sparse, studies on isolated vessels and cells have suggested their involvement in renal vasoregulation. Renal blood flow (RBF) is an essential determinant of kidney function, including glomerular filtration, water and solute reabsorption, and waste product excretion. Functional alterations in ion channels that are expressed in the endothelium and smooth muscle of renal vessels can modulate renal vascular resistance, arterial pressure, and RBF. Hence, renal vascular TRP channels are potential therapeutic targets for the treatment of kidney disease. This review summarizes the current knowledge of TRP channel expression in renal vasculature and their role in controlling kidney function in health and disease.

Kristal O’Brien,1,2 Sayanthooran Saravanabavan,1,2 Jennifer QJ Zhang,1,2 Annette TY Wong,1,2 Alexandra Munt,1,2 Jane S Burgess,1,2 Gopala K Rangan1,2 1Centre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia; 2Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Sydney, New South Wales, AustraliaCorrespondence: Gopala K RanganCentre for Transplant and Renal Research, Westmead Institute for Medical Research, The University of Sydney, Level 5, 176 Hawkesbury Road (PO Box 412), Westmead, NSW 2145, AustraliaTel +61-2 8627 3502Fax +61-2 9475-1146Email g.rangan@sydney.edu.auBackground/Aim: The natural history of the renal microvasculature changes in PKD is not known. The aim of this study was to test the hypothesis that angiogenesis is coupled with kidney cyst expansion, and the loss of peritubular capillary networks precedes the onset of interstitial fibrosis.Methods: The renal microvasculature (RECA-1 and CD34) was evaluated in groups of Lewis polycystic kidney (LPK) rats and juvenile cystic kidney (jck) mice during the early, mid and late stage of disease. In addition, LPK rats and jck mice received sirolimus to determine if the reduction in renal cyst growth is in part mediated by the suppression of angiogenesis.Results: In LPK rats, the loss of peritubular capillaries occurred in early-stage disease and paralleled cyst formation whereas in jck mice it was delayed to the mid stage. In both models, vasa recta were displaced by growing cysts and regressed in LPK rats with disease progression but lengthened in jck mice. Cortical and medullary capillary neoangiogenesis occurred during the early stage in both models and persisted with progression. Treatment with sirolimus reduced cyst enlargement but did not alter the progression of renal microvasculature changes in either model.Conclusion: Regression of peritubular capillaries and disruption of vasa recta occur in parallel with angiogenesis and the progressive enlargement of kidney cysts. These data suggest that the regrowth of peritubular capillaries together with inhibition of angiogenesis are potential strategies to be considered in the treatment of PKD.Keywords: juvenile cystic kidney, jck, Lewis polycystic kidney, LPK, peritubular capillary loss, renal vasculature

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.

Given the relevance of the inextricable coupling between microcirculation and physiology, and the relation to organ function and disease progression, the construction of synthetic vascular networks for mathematical modelling and computer simulation is becoming an increasingly broad field of research. Building vascular networks that mimic in vivo morphometry is feasible through algorithms such as constrained constructive optimization (CCO) and variations. Nevertheless, these methods are limited by the maximum number of vessels to be generated due to the whole network update required at each vessel addition. In this work, we propose a CCO-based approach endowed with a domain decomposition strategy to concurrently create vascular networks. The performance of this approach is evaluated by analysing the agreement with the sequentially generated networks and studying the scalability when building vascular networks up to 200 000 vascular segments. Finally, we apply our method to vascularize a highly complex geometry corresponding to the cortex of a prototypical human kidney. The technique presented in this work enables the automatic generation of extensive vascular networks, removing the limitation from previous works. Thus, we can extend vascular networks (e.g. obtained from medical images) to pre-arteriolar level, yielding patient-specific whole-organ vascular models with an unprecedented level of detail.

Three-dimensional (3D) printed model of the renal vasculature shows a high level of accuracy of subsequent divisions of both the arterial and the venous tree. However, minor artifacts appeared in the form of oval endings to the terminal branches of the vascular tree, contrary to the anticipated sharply pointed segments. Unfortunately, selective laser sintering process does not currently permit to present the arterial, venous and urinary systems in distinct colors, hence topographic relationship between the vascular and the pelvicalyceal systems is difficult to attain. Nonetheless, the 3D printed model can be used for educational purposes to demonstrate the vast renal vasculature and may also serve as a reference model whilst evaluating morphological anomalies of the intrarenal vasculature in a surgical setting. [ABSTRACT FROM AUTHOR]

Abstract The GLP‐1 receptor (GLP‐1R) in the kidney is expressed exclusively in vascular smooth muscle cells in arteries and arterioles. Downstream effects of the activation of the renal vascular GLP‐1R are elusive but may involve regulation of the renin‐angiotensin‐aldosterone system (RAAS). The expression of Ren1 in the mouse renal vasculature was investigated by in situ hybridization after a single subcutaneous dose of liraglutide, semaglutide and after repeated injections of liraglutide. Single and repeated exposure to GLP‐1R agonists induced expression of Ren1 in the renal vascular smooth muscle cell compartment compared with vehicle injected controls (p

The GLP‐1 receptor (GLP‐1R) in the kidney is expressed exclusively in vascular smooth muscle cells in arteries and arterioles. Downstream effects of the activation of the renal vascular GLP‐1R are elusive but may involve regulation of the renin‐angiotensin‐aldosterone system (RAAS). The expression of Ren1 in the mouse renal vasculature was investigated by in situ hybridization after a single subcutaneous dose of liraglutide, semaglutide and after repeated injections of liraglutide. Single and repeated exposure to GLP‐1R agonists induced expression of Ren1 in the renal vascular smooth muscle cell compartment compared with vehicle injected controls (p <.0001) for both semaglutide and liraglutide. The present data show a robust induction of Ren1 expression in the vascular smooth muscle cells of the kidney after single and repeated GLP‐1R activation and this renin recruitment may be involved in the effects of GLP‐1R agonist treatment on kidney disease. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to assess the relationship between renal artery cross-section area and kidney volume with consideration of anatomical variants of renal arteries, sexual dimorphism and lateralisation.Materials and Methods: Two hundred and two patients, 104 women and 98 men, aged 57.3 ± 16 years were examined using computed tomography angiography (CTA) of abdominal aorta for various reasons. The cross-section areas of renal arteries were measured automatically with a vessel tracking programme and summed up on each side in case of the presence of additional renal arteries. The kidneys were measured manually.Results: Additional renal arteries (ARA) were found in 68 (33.7%) patients. Fifty-three (77.9%) of them had one, 11 (16.2%) two and 4 (5.9%) three ARAs. Bilateral ARAs occurred in 10 cases (14.7% patients with ARA). Proximal branching of renal artery occurred in 36 (8.4%) renal arteries. The cross-section area of the largest renal artery depended on the number of ipsilateral renal arteries. Mean cross-section area of the main left renal artery was larger than on the right side (28.52 mm2 vs. 25.36 mm2, p < 0.01) in the whole analysed group. Strong sexual dimorphism in renal artery cross-section area was observed (p < 0.01) in favour of men (31.3 mm2 in men and 22.9 mm2 in women). Mean total renal artery cross-section area has positively correlated with kidney volume (p < 10-13) in both sexes with Pearson correlation value of 0.5.Conclusions: The cross-section area of renal arteries correlated positively with kidney volume in both sexes. Presence of ARAs does not influence the sum of cross-section areas of renal arteries. In case of a difference between left and right renal artery cross-section area with symmetrical kidneys, it is necessary to look for ARA. [ABSTRACT FROM AUTHOR]

Assumptions surrounding the kidney as a target for accumulation of ochratoxin A (OTA) are addressed because the contribution of the toxin in blood seems invariably to have been ignored. Adult rats were maintained for several weeks on toxin-contaminated feed. Using standard perfusion techniques, animals were anaesthetised, a blood sample was taken, one kidney was ligated, and the other kidney perfused with physiological saline in situ under normal blood pressure. Comparative analysis of OTA in pairs of kidneys showed marked reduction in the perfused organ in the range 37%–98% (mean 75%), demonstrating the general efficiency of perfusion supported also by histology, and implying a major role of blood in the total OTA content of kidney. Translation of OTA values in plasma to whole blood, and its predicted contribution as a 25% vascular compartment in kidney gave values similar to those in non-perfused kidneys. Thus, apparent ‘accumulation’ of OTA in kidney is due to binding to plasma proteins and long half-life in plasma. Attention should be re-focused on whole animal pharmacokinetics during chronic OTA exposure. Similar principles may be applied to DNA-OTA adducts which are now recognised as occurring in blood; application could also extend to other nephrotoxins such as aristolochic acid. Thus, at least, quantitative reassessment in urological tissues seems necessary in attributing adducts specifically as markers of potentially-tumourigenic exposure.

Kidney development involves reciprocal and inductive interactions between the ureteric bud (UB) and surrounding metanephric mesenchyme. Signals from renal stromal lineages are essential for differentiation and patterning of renal epithelial and mesenchymal cell types and renal vasculogenesis; however, underlying mechanisms remain not fully understood. Integrin-linked kinase (ILK), a key component of integrin signaling pathway, plays an important role in kidney development. However, the role of ILK in renal stroma remains unknown. Here, we ablated ILK in renal stromal lineages using a platelet-derived growth factor receptor B (Pdgfrb)-Cre mouse line, and the resulting Ilk mutant mice presented postnatal growth retardation and died within 3 wk of age with severe renal developmental defects. Pdgfrb-Cre;Ilk mutant kidneys exhibited a significant decrease in UB branching and disrupted collecting duct formation. From E16.5 onward, renal interstitium was disorganized, forming medullary interstitial pseudocysts. Pdgfrb-Cre;Ilk mutants exhibited renal vasculature mispatterning and impaired glomerular vascular differentiation. Impaired glial cell-derived neurotrophic factor/Ret and bone morphogenetic protein 7 signaling pathways were observed in Pdgfrb-Cre;Ilk mutant kidneys. Furthermore, phosphoproteomic and Western blot analyses revealed a significant dysregulation of a number of key signaling pathways required for kidney morphogenesis, including PI3K/AKT and MAPK/ERK in Pdgfrb-Cre;Ilk mutants. Our results revealed a critical requirement for ILK in renal-stromal and vascular development, as well as a noncell autonomous role of ILK in UB branching morphogenesis. [ABSTRACT FROM AUTHOR]

Noninvasive imaging of the kidney vasculature in preclinical murine models is important for the assessment of renal development, studying diseases and evaluating new therapies but is challenging to achieve using existing imaging modalities. Photoacoustic imaging is a promising new technique that is particularly well suited to visualizing the vasculature and could provide an alternative to existing preclinical imaging methods for studying renal vascular anatomy and function. To investigate this, an all-optical Fabry-Perot-based photoacoustic scanner was used to image the abdominal region of mice. High-resolution three-dimensional, noninvasive, label-free photoacoustic images of the mouse kidney and renal vasculature were acquired in vivo. The scanner was also used to visualize and quantify differences in the vascular architecture of the kidney in vivo due to polycystic kidney disease. This study suggests that photoacoustic imaging could be utilized as a novel preclinical imaging tool for studying the biology of renal disease. [ABSTRACT FROM AUTHOR]

Introduction: Variations of the renal arteries have been studied and published across various population groups, but similar information for the ethnically diverse nation of Australia is lacking. This study describes the pattern of renal artery anomalies in a section of the Australian population based on computed tomography (CT) angiograms of the abdomen and cadaveric dissection.Methods: The renal arterial vasculature of 594 kidneys from 300 subjects (28 cadavers, 272 CT) was studied. The number and pattern of renal arteries were categorised on the basis of laterality, point of origin and termination in the kidney (superior pole, hilum and inferior pole), symmetry and sex.Results: Multiple renal arteries were discovered in 22% of subjects and 12.12% of kidneys. The most common pattern observed was the presence of one variant renal artery (93.1%), compared to the finding of two (5.6%) and three (1.4%) multiple arteries. The aorta was the most frequent site of origin for anomalous vessels, while the hilum was the predominant point of entry. No significant difference was established between left- and right-sided kidneys (13.8% vs. 12.5%; P = 0.627); however, unilateral distribution was more common than bilateral additional renal arteries (16.7% vs. 3.4%; P < 0.01), and variations among males were more than females (27.2% vs. 15.2%; P < 0.05). A higher rate of multiple renal arteries was noted in cadaveric dissections compared to CT images (46.4% vs. 19.5%; P < 0.01).Conclusion: These findings provide application of an evidence-based teaching tool that facilitates education regarding renal arterial variations in Australia. [ABSTRACT FROM AUTHOR]

Aims: To test the suggested association of low nephron number and later development of renal and cardiovascular disease we investigated the effects of high sodium diet in heterozygous GDNF+/- mice. Methods: Aged wild type and GDNF+/- mice were grouped together according to high sodium (HS, 4%) or low sodium (LS, 0.03%) diet for 4 weeks. The heart, the aorta and the kidneys were processed for morphometric and stereological evaluations and TaqMan PCR. Results: On HS GDNF+/- mice showed significantly higher drinking volume and urine production than wt and mean arterial blood pressure tended to be higher. Heart weight was higher in GDNF+/- than in wt, but the difference was only significant for LS. HS significantly increased cardiac interstitial tissue in GDNF+/-, but not in wt. On LS GDNF+/- mice had significantly larger glomeruli than wt and HS led to an additional two fold increase of glomerular area compared to LS. On electron microscopy glomerular damage after HS was seen in GDNF+/-, but not in wt. Dietary salt intake modulated renal IL-10 gene expression in GDNF+/-. Conclusion: In the setting of 30% lower nephron number HS diet favoured maladaptive changes of the kidney as well as of the cardiovascular system.

ABSTRACT The renal anatomy and its development is complex. This complexity is associated with numerous variations. Each renal variation has its own clinical and surgical importance. There is a good correlation between the ascent of the kidney, the level of its origin and number of the renal arteries. Any anomaly in the renal artery development may be due to a delay in the kidney ascension and it can lead to an ectopic kidney. Ectopic kidneys are more frequent in males and they are observed commonly on the left side. In the present study, we came across a rare case of a unilateral right renal ectopia and bilateral multiple renal arteries, with 5 renal arteries on the right side and 2 on the left side. The renal veins were 3 on the right side and two on the left side, with the retro aortic left renal vein, which were observed during the routine dissection of a male cadaver. This observation would be of immense importance for surgeons, interventional radiologists, nephrologists and vascular surgeons.

Vascular anatomical variations are not uncommon and may affect any organ's arterial or venous vasculature. The coexistence of variations in different organic systems is less commonly found, but of great clinical significance in a series of clinical conditions like organ transplantation and surgical preoperative planning. Multidetector computed tomography angiography (MDCTA) has emerged as a valuable alternative to the conventional angiography for accurate evaluation of vascular anatomy and pathology. Radiologists should be familiar with each organ's vascular variations and always report them to the clinician, even if they represent an incidental finding. This case report presents a 52-year-old female patient undergoing abdominal MDCTA for characterization of a renal lesion. This examination revealed the presence of three hilar arteries on the left kidney, a main renal vein in combination with an additional renal vein in both sides along with a replaced right hepatic artery originating from the superior mesenteric artery. Moreover, both inferior phrenic arteries were found originating from the coeliac axis. 3D volume rendering technique images were used in the evaluation of vascular anatomy as illustrated in this case report. [ABSTRACT FROM AUTHOR]

Although serotonin has been shown to inhibit peripheral sympathetic outflow, serotonin regulation on renal sympathetic outflow has not yet been elucidated. This study investigated which 5-HT receptor subtypes are involved. Wistar rats were anesthetized (sodium pentobarbital; 60 mg/kg, i.p.), and prepared for in situ autoperfused rat kidney, which allows continuous measurement of systemic blood pressure (SBP), heart rate (HR) and renal perfusion pressure (PP). Electrical stimulation of renal sympathetic nerves resulted in frequency-dependent increases in PP (18.3 ± 1.0, 43.7 ± 2.7 and 66.7 ± 4.0 for 2, 4 and 6 Hz, respectively), without altering SBP or HR. 5-HT, 5-carboxamidotryptamine (5-HT 1/7 agonist) (0.00000125–0.1 μg/kg each) or l -694,247 (5-HT 1D agonist; 0.0125 μg/kg) i.a. bolus inhibited vasopressor responses by renal nerve electrical stimulation, unlike i.a. bolus of agonists α-methyl-5-HT (5-HT 2 ), 1-PBG (5-HT 3 ), cisapride (5-HT 4 ), AS-19 (5-HT 7 ), CGS-12066B (5-HT 1B ) or 8-OH-DPAT (5-HT 1A ) (0.0125 μg/kg each). The effect of l -694,247 did not affect the exogenous norepinephrine-induced vasoconstrictions, whereas was abolished by antagonist LY310762 (5-HT 1D ; 1 mg/kg) or l -NAME (nitric oxide; 10 mg/kg), but not by indomethacin (COX 1/2 ; 2 mg/kg) or glibenclamide (ATP-dependent K + channel; 20 mg/kg). These results suggest that 5-HT mechanism-induced inhibition of rat vasopressor renal sympathetic outflow is mainly mediated by prejunctional 5-HT 1D receptors via nitric oxide release. [ABSTRACT FROM AUTHOR]

Background: Na/Ca exchanger 1 (NCX1) controls intracellular Ca concentration in various cell types. In the kidney, NCX1 is expressed mainly in the distal tubular basolateral membrane as well as in vascular smooth muscle. Tubular NCX1 is involved in Ca reabsorption, and NCX1 in renal arterioles may control intraglomerular pressure. However, the functions of renal NCX1 have not been studied in vivo. Therefore, this study examined the effects of renal NCX1 blockade on water and solute metabolism, renal function and blood pressure in rats. Methods: Wistar-Kyoto rats were uninephrectomized, and an osmotic mini pump was implanted to infuse the remnant kidney cortex with a specific NCX1 inhibitor, SEA0400 (SEA), or vehicle for 7 days. Results: Serum Ca concentration and urinary Ca excretion were similar between the vehicle- and SEA-treated groups. However, serum phosphate was significantly decreased by 8 % in the SEA group, with similar urinary phosphate excretion between the two groups. Systolic blood pressure was higher in the SEA group (117 ± 3 vs. 126 ± 1 mmHg, n = 9-11), with a 1.6-fold increase in plasma aldosterone concentration. However, SEA significantly reduced urinary protein excretion and the glomerular sectional area by 16 and 8 %, respectively. Similar experiment in spontaneously hypertensive rats produced different results. Conclusion: Renal SEA treatment reduced serum phosphate concentration, urinary protein and glomerular size with higher systemic blood pressure compared to control Wistar-Kyoto rats. Further study on renal NCX1 may be beneficial in delineating the pathophysiology of glomerular pressure control and calcium/phosphate regulations. [ABSTRACT FROM AUTHOR]

The kidney is vulnerable to hypoxia, and substantial efforts have been made to ameliorate renal ischemic injury secondary to pathological conditions. Stimulation of the nitrate–nitrite–nitric oxide pathway is associated with renal and cardiovascular protection in disease models, but less is known about the vascular effects during renal ischemia. This study was aimed at investigating the vascular effects of nitrite in the kidney during normoxic and ischemic conditions. Using a multiwire myograph system, we assessed nitrite-mediated relaxation (10 −9 –10 −4 mol/L) in isolated and preconstricted renal interlobar arteries from C57BL/6 mice under normal conditions ( p O 2 13 kPa; pH 7.4) and with low oxygen tension and low pH to mimic ischemia ( p O 2 3 kPa; pH 6.6). Xanthine oxidoreductase expression was analyzed by quantitative PCR, and production of reactive nitrogen species was measured by DAF-FM DA fluorescence. During normoxia significant vasodilatation (15±3%) was observed only at the highest concentration of nitrite, which was dependent on NO–sGC–cGMP signaling. The vasodilatory responses to nitrite were greatly sensitized and enhanced during hypoxia with low pH, demonstrating significant dilatation (11±1%) already in the physiological range (10 −8 mol/L), with a maximum response of 27±2% at 10 −4 mol/L. In contrast to normoxia, and to that observed with a classical NO donor (DEA NONOate), this sensitization was independent of sGC–cGMP signaling. Moreover, inhibition of various enzymatic systems reported to reduce nitrite in other vascular beds, i.e., aldehyde oxidase (raloxifene), aldehyde dehydrogenase (cyanamide), and NO synthase (L-NAME), had no effect on the nitrite response. However, inhibition of xanthine oxidoreductase (XOR; febuxostat or allopurinol) abolished the sensitized response to nitrite during hypoxia and acidosis. In conclusion, in contrast to normoxia, nitrite exerted potent vasorelaxation during ischemic conditions already at physiological concentrations. This effect was dependent on functional XOR but independent of classical downstream signaling by sGC–cGMP. [ABSTRACT FROM AUTHOR]

Assumptions surrounding the kidney as a target for accumulation of ochratoxin A (OTA) are addressed because the contribution of the toxin in blood seems invariably to have been ignored. Adult rats were maintained for several weeks on toxin-contaminated feed. Using standard perfusion techniques, animals were anaesthetised, a blood sample was taken, one kidney was ligated, and the other kidney perfused with physiological saline in situ under normal blood pressure. Comparative analysis of OTA in pairs of kidneys showed marked reduction in the perfused organ in the range 37%-98% (mean 75%), demonstrating the general efficiency of perfusion supported also by histology, and implying a major role of blood in the total OTA content of kidney. Translation of OTA values in plasma to whole blood, and its predicted contribution as a 25% vascular compartment in kidney gave values similar to those in non-perfused kidneys. Thus, apparent 'accumulation' of OTA in kidney is due to binding to plasma proteins and long half-life in plasma. Attention should be re-focused on whole animal pharmacokinetics during chronic OTA exposure. Similar principles may be applied to DNA-OTA adducts which are now recognised as occurring in blood; application could also extend to other nephrotoxins such as aristolochic acid. Thus, at least, quantitative reassessment in urological tissues seems necessary in attributing adducts specifically as markers of potentially-tumourigenic exposure. [ABSTRACT FROM AUTHOR]

The mechanisms responsible for the gender difference in blood pressure ( BP) in humans are not clear. Over the past several years we have studied the spontaneously hypertensive rat ( SHR) as a model of sex differences in BP control. In the present study, we tested the hypothesis that renal vascular and microsomal epoxyeicosatrienoic acid ( EET) levels are higher in females than males, and increasing vascular EETs by blocking epoxide hydrolase with AUDA will reduce BP more in males than females. Renal vascular and microsomal EETs were higher in female SHR than males. Mean arterial pressure ( MAP by telemetry) was higher in males than females during the baseline period of 6 days, and although the epoxide hydrolase inhibitor, AUDA, given for 10 days increased renal microvascular EETs in both groups, AUDA did not affect MAP in either group. These data suggest that EETs do not contribute to the sex differences in hypertension in young SHR. [ABSTRACT FROM AUTHOR]

Aims: To test the suggested association of low nephron number and later development of renal and cardiovascular disease we investigated the effects of high sodium diet in heterozygous GDNF+/- mice. Methods: Aged wild type and GDNF+/- mice were grouped together according to high sodium (HS, 4%) or low sodium (LS, 0.03%) diet for 4 weeks. The heart, the aorta and the kidneys were processed for morphometric and stereological evaluations and TaqMan PCR. Results: On HS GDNF+/- mice showed significantly higher drinking volume and urine production than wt and mean arterial blood pressure tended to be higher. Heart weight was higher in GDNF+/- than in wt, but the difference was only significant for LS. HS significantly increased cardiac interstitial tissue in GDNF+/-, but not in wt. On LS GDNF+/- mice had significantly larger glomeruli than wt and HS led to an additional two fold increase of glomerular area compared to LS. On electron microscopy glomerular damage after HS was seen in GDNF+/-, but not in wt. Dietary salt intake modulated renal IL-10 gene expression in GDNF+/-. Conclusion: In the setting of 30% lower nephron number HS diet favoured maladaptive changes of the kidney as well as of the cardiovascular system. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is nowadays considered as a potential cardiovascular and renal risk factor. We tested the hypotheses that vitamin D deficiency impairs the endothelial function of renal vasculature and whether vitamin D levels and endothelial function can be improved by the treatment with statins. Methods: In a double-blind, randomized study of 31 hypercholesterolemic patients with vitamin D insufficiency (<30 ng/ml) were randomly assigned to rosuvastatin (10 mg/d) and placebo for 6 weeks. Basal nitric oxide (NO) activity of the renal vasculature was assessed both before and after the blockade of NO synthases with systemic infusion of N(G)-monomethyl- l-arginine ( l-NMMA). In parallel, 25(OH)D was measured. Results: Multiple regression analysis revealed that at baseline 25(OH)D is an independent determinant of basal NO activity as assessed by the decrease in RPF, in response to l-NMMA ( β = −0.446, r = 0.015). Compared to placebo treatment, rosuvastatin increased 25(OH)D levels (21.6 ± 4.0 vs. 24.1 ± 8.1 ng/ml, p = 0.039). Basal NO activity was significantly more increased after 6-week therapy with rosuvastatin than with placebo (−94.8 ± 70 vs. −68.2 ± 32 ml/min, p = 0.044), indicating increased basal NOS activity after 6 weeks of rosuvastatin treatment. Basal NO activity in the placebo phase was correlated inversely with 25(OH)D ( r = −0.385; p = 0.027). Conclusions: Thus, vitamin D insufficiency is associated with impaired endothelial function in the renal vasculature and both were beneficially influenced by the treatment with rosuvastatin. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether PGI2 would be evoked by the endogenous endothelial B2 receptor agonist bradykinin (BK) in the porcine interlobular renal artery and, if so, to determine how it would influence the vasomotor reaction, and the specific cyclooxygenase (COX) isoform(s) involved in its synthesis. The production of the PGI2 metabolite 6-keto-PGF1α was analyzed with HPLC-mass spectroscopy, while vasomotor reaction to PGI2 or BK was determined with isometric force measurement. Results showed that BK evoked an increase in the production of 6-keto-PGF1α, which was abolished by endothelial denudation that removed COX-1 expression, or was reduced by COX-1 inhibition. Interestingly, PGI2 evoked a potent contraction, which was prevented by antagonizing thromboxane-prostanoid (TP) receptors and was not enhanced by antagonizing the vasodilator PGI2 (IP) receptors. The IP receptor agonists MRE-269 and iloprost did not induce any relaxation. Moreover, iloprost, which is also a PGI2 analog, caused a contraction, which was sensitive to TP receptor antagonism, but was to a significantly lesser extent than that of PGI2. Indeed, IP receptors were not detected by RT-PCR or Western blotting in the vessel. Following nitric oxide synthase (NOS) inhibition, BK also evoked an endothelium-dependent contraction, which was blocked by TP receptor antagonism. In addition, inhibition of COX-1 (but not COX-2) impeded the vasoconstrictor activity of BK and expedited the relaxation induced by the agonist in NOS-intact vessels. These results demonstrate that in the porcine interlobular renal artery BK evokes endothelial COX-1-mediated PGI2 synthesis, which mainly leads to the activation of TP receptors and a vasoconstrictor response, possibly due to a scarcity of vasodilator activity mediated by IP receptors. Also, our data suggested that the effect of a PGI2 analog on TP receptors could be reduced compared with that of PGI2 due to modified structure as with iloprost. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal α1-adrenoceptor subtype composition. Methods: In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na+ (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (α-adrenoceptor agonist), phenylephrine (α1-adrenoceptor agonist) and methoxamine (α1A-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca2+ channel blocker), 5-methylurapidil (α1A-adrenoceptor antagonist), chloroethylclonidine (α1B-adrenoceptor antagonist) and BMY 7378 (α1D-adrenoceptor antagonist). Results: In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses. Conclusion: The data demonstrated that there was a functional coexistence of α1A- and α1D-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic α-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The purpose of this study is to describe the anatomy and obtain echographic measurements of normal kidneys in brown lemurs (Eulemur fulvus). The anatomical findings show that brown lemur kidneys are comparable to those of rats except for an elongated papilla. The kidneys of 16 (7 females and 9 males) lemurs were examined with two-dimensional and power Doppler ultrasonography under general anesthesia. Morphometrically, the left and right kidney surface areas are comparable (3.29 and 3.51 cm2). Kidney area has a significant linear correlation with body weight. Echo-Doppler findings show that the mean renal arterial blood flow speeds for the left and right kidneys are comparable (0.70 and 0.73 m/s). However, flow speed is higher in the male (0.79 m/s) than in the female (0.60 m/s). The renal arterial diameters are between 1.0 and 1.8 mm. The fact that anesthesia can have hemodynamic effects on renal vasculature should be taken into consideration when assessing these echographic results. Am. J. Primatol. 71:647–653, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Angiotensin II is known to act primarily on the angiotensin AT1 receptors to mediate its physiological and pathological actions. Des-aspartate-angiotensin I (DAA-I) is a bioactive angiotensin peptide and have been shown to have contrasting vascular actions to angiotensin II. Previous work in this laboratory has demonstrated an overwhelming vasodepressor modulation on angiotensin II-induced vasoconstriction by DAA-I. The present study investigated the involvement of the AT1 receptor in the actions of DAA-I on angiotensin II-induced vascular actions in the renal vasculature of normotensive Wistar–Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and streptozotocin (STZ)-induced diabetic rats. The findings revealed that the angiotensin receptor in rat kidney homogenate was mainly of the AT1 subtype. The AT1 receptor density was significantly higher in the kidney of the SHR. The increase in AT1 receptor density was also confirmed by RT-PCR and Western blot analysis. In contrast, AT1 receptor density was significantly reduced in the kidney of the streptozotocin-induced diabetic rat. Perfusion with 10−9 M DAA-I reduced the AT1 receptor density in the kidneys of WKY and SHR rats suggesting that the previously observed vasodepressor modulation of the nonapeptide could be due to down-regulation or internalization of AT1 receptors. RT-PCR and Western blot analysis showed no significant changes in the content of AT1 receptor mRNA and protein. This supports the suggestion that DAA-I causes internalization of AT1 receptors. In the streptozotocin-induced diabetic rat, no significant changes in renal AT1 receptor density and expression were seen when its kidneys were similarly perfused with DAA-I. [Copyright &y& Elsevier]

Endothelial dysfunction and increased oxidative stress contribute to the progression of diabetic nephropathy. To analyze the functional significance of the G894T polymorphism of NOS3, the gene encoding endothelial nitric oxide synthase (NOS), we assessed basal nitric oxide activity and the amount of oxidative stress in the renal circulation of patients with type 2 diabetes.Renal plasma flow (RPF) was assessed by steady-state input clearance technique with sodium para-aminohippurate in 84 patients with type 2 diabetes and 84 patients without diabetes. RPF was measured at baseline and after the infusion of the NOS inhibitor N-monomethyl-L-arginine (4.25 mg/kg); the substrate of NOS L-arginine (100 mg/kg); and coinfusion of vitamin C (3 g) with L-arginine (100 mg/kg).The decrease of RPF to N-monomethyl-L-arginine was similar between carriers of the T allele and homozygous carriers of the G allele in patients with diabetes (-56±40 vs. -68.1±74 ml/min/1.73 m2, P=0.342) and patients without diabetes (-66.7±81 vs. -58.3±63 ml/min/1.73 m2, P=0.606). In patients with diabetes, however, carriers of the T allele revealed a more pronounced increase of RPF to coinfusion of vitamin C with L-arginine than homozygous carriers of the G allele (61.8±75 vs. 22.3±73 ml/min/1.73 m2, P=0.021), whereas in patients without diabetes the response of RPF to coinfusion of vitamin C with L-arginine was similar between both groups (46.2±80 vs. 70.7±86 ml/min/1.73 m2, P=0.217). Gene-environment interaction between disease (diabetes) and genotype (genotype GG vs. genotype GT/TT) was observed for increase of RPF to coinfusion of vitamin C with L-arginine (P=0.020).G894T polymorphism of NOS3 has no impact on the basal nitric oxide activity of renal circulation. In contrast, the T allele is associated with increased oxidative stress in the renal circulation in patients with diabetes suggesting a specific role of the G894T polymorphism in the pathogenesis of diabetic nephropathy. [ABSTRACT FROM AUTHOR]

1 The present study investigated the effect of streptozotocin-induced diabetes on α1-adrenoceptor subtypes in rat renal resistance vessels. 2 Studies on renal haemodynamics were carried out 7 days after the last streptozotocin. Changes in renal blood flow were recorded in response to electrical stimulation of the renal nerve (RNS) and a range of adrenergic agonists; noradrenaline (NA), phenylephrine (PE) and methoxamine (MTX), either in the absence or the presence of nitrendipine (Nit), 5-methylurapidil (MEU), chlorethylclonidine (CEC) or BMY 7378. 3 In non-diabetic animals, Nit, MEU and BMY 7378 significantly attenuated renal vasoconstriction induced by adrenergic agonists, while CEC showed a significant accentuation in RNS-induced responses without having a significant effect on responses to adrenergic agonists. In diabetic rats, renal vasoconstriction was also significantly reduced in Nit-, MEU- and BMY 7378-treated groups and CEC potentiated RNS-induced contractions caused a change similar to that observed in non-diabetic rats. BMY 7378 significantly ( P < 0.05) attenuated the PE- and MTX-induced vasoconstrictions but did not cause any significant ( P > 0.05) alteration in the RNS- and NA-induced responses. 4 The results showed functional co-existence of α1A- and α1D-adrenoceptors in the renal vasculature of SD rats irrespective of the presence of diabetes. A possible minor contribution of prejunctional α-adrenoceptor subtype has also been suggested in either experimental group, particularly possible functional involvement of α1B-adrenoceptor subtypes in non-diabetic SD rats. [ABSTRACT FROM AUTHOR]