Diadenosine pentaphosphate modulates glomerular arteriolar tone and glomerular filtration rate.

INTRODUCTION: Mechanisms and participating substances involved in the reduction of glomerular filtration (GFR) in contrast-induced acute kidney injury (CI-AKI) are still matter of debate. We hypothesized that diadenosine polyphosphates are released by the action of contrast media on tubular cells and may act on glomerular arterioles and reduce GFR. METHODS: Freshly isolated rat tubules were treated with the contrast medium iodixanol (47 mg iodine per mL) at 37 °C for 20 min. The content of Apn A (n = 3-6) in the supernatant of treated tubules and in the plasma of healthy persons and patients with AKI was analysed using reversed-phase chromatography, affinity chromatography and mass spectrometry. GFR was obtained in conscious mice by inulin clearance. Concentration response curves for Apn A (n = 3-6, 10(-12) -10(-5)  mol L(-1) ) were measured in isolated perfused glomerular arterioles. RESULTS: Iodixanol treatment of tubules significantly increased the concentration of Apn A (n = 3-5) in the supernatant. Ap6 A was below the detection limit. AKI patient shows higher concentrations of Apn A compared to healthy. Application of Ap5 A significantly reduced the GFR in conscious mice. Ap5 A reduced afferent arteriolar diameters, but did not influence efferent arterioles. The constrictor effect on afferent arterioles was strong immediately after application, but weakened with time. Then, non-selective P2 inhibitor suramin blocked the Ap5 A-induced constriction. CONCLUSION: The data suggest that Ap5 A plays a role in the pathophysiology of CI-AKI. We show a contrast media-induced release of Ap5 A from tubules, which might increase afferent arteriolar resistance and reduce the GFR.

The neurovascular unit - concept review.

The cerebral hyperaemia is one of the fundamental mechanisms for the central nervous system homeostasis. Due also to this mechanism, oxygen and nutrients are maintained in satisfactory levels, through vasodilation and vasoconstriction. The brain hyperaemia, or coupling, is accomplished by a group of cells, closely related to each other; called neurovascular unit (NVU). The neurovascular unit is composed by neurones, astrocytes, endothelial cells of blood-brain barrier (BBB), myocytes, pericytes and extracellular matrix components. These cells, through their intimate anatomical and chemical relationship, detect the needs of neuronal supply and trigger necessary responses (vasodilation or vasoconstriction) for such demands. Here, we review the concepts of NVU, the coupling mechanisms and research strategies.

Functional characterization of isolated, perfused outermedullary descending human vasa recta.

AIM: The renal medulla plays an important role in the control of water and salt balance by the kidney. Outer medullary descending vasa recta (OMDVR) are microscopic vessels providing blood flow to the renal medulla. Data on the physiology of human vasa recta are scarce. Therefore, we established an experimental model of human single isolated, perfused OMDVR and characterized their vasoactivity in response to angiotensin II and to pressure changes. METHODS: Human non-malignant renal tissue was obtained from patients undergoing nephrectomy due to renal cell carcinoma. OMDVR were dissected under magnification and perfused using concentric microscopic pipettes. The response of OMDVR to angiotensin II and pressure changes was quantified in serial pictures. All patients signed a consent form prior to surgery. RESULTS: Outer medullary descending vasa recta constricted significantly after bolus applications of angiotensin II. OMDVR constriction to angiotensin II was also concentration dependent. Response to luminal pressure changes was different according to the diameter of vessels, with larger OMDVR constricting after pressure increase, while smaller ones did not. CONCLUSION: Outer medullary descending vasa recta constrict in response to angiotensin II and pressure increases. Our results show that OMDVR may take part in the regulation of medullary blood flow in humans. Our model may be suitable for investigating disturbances of renal medullary circulation in human subjects.