In a previous study of the changes in glomerular structure in the isolated perfused kidney (IPK), perfusion at high pressures lead to an enlargement of the glomerular tuft and to the formation of giant capillaries. The present paper analyzes the morphological and dimensional changes of the peripheral glomerular capillary wall under these circumstances. The enlargement of glomerular capillaries at high pressure perfusion was accompanied by a considerable increase in the surface area of the glomerular basement membrane (GBM). The podocyte as well as the endothelial layer perfectly adapted to the acute challenge in covering increasing GBM area. The interdigitating foot process pattern showed up in an ideal arrangement. The capillary wall expansion was associated with a significant increase in total pericapillary slit area. Compared to the corresponding low pressure groups (65 mm Hg, without and with the application of vasodilators) the slit area increased in the high pressure groups (105 mm Hg, without and with vasodilator) by approximately 50 and 75%, respectively. This increase of the slit area was mainly due to an increase in slit length; the slit width remained fairly constant. These findings indicate that the pericapillary wall is distensible based on a distensibility of the GBM. We suggest that the contractile apparatus of podocyte foot processes regulates the expansion of the GBM.

Background: Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo-and radiotherapy in vitro.

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Thin sections and freeze-fracture replicas were used to investigate the ultrastructural changes associated with renin secretion from the juxtaglomerular part of the afferent arteriole of male mice. Adrenalectomized animals in which renin secretion was stimulated by furosemide application and bleeding were also studied. Exocytosis of mature electron-dense granules was found in all experimental groups. Before extrusion, the region of granule facing the cell membrane changed, with vesicular and/or stacked membrane-like profiles and a small local protrusion of the granule membrane appearance of. Concomitantly, punctuate sites of fusion between the cell and granule membranes were observed. Later, unaltered amorphous, and altered membrane-like granule content was released from omega-shaped cavities into the extracellular space. In stimulated animals the alteration and extrusion of several closely apposed granules was reminiscent of compound exocytosis. Coated pits were frequently seen, suggesting specific retrieval of the former granule membrane. The collapsing silhouette of a depleted granule very rarely took the form of a saccule whose narrow membrane-bounded neck was continuous with the extracellular space. Observed were two additional events by which active and inactive renin may be released. Small electron-lucent vacuoles of undetermined origin fused with the cell membrane and, in stimulated kidneys, some epithelioid cell processes disintegrated. However, the interpretation of the related ultrastructural phenomena was uncertain.

L‐selectin belongs to the C‐type lectin family of glycoproteins and is constitutively expressed on most leukocytes. L‐selectin mediates leukocyte rolling in inflamed microvessels and high endothelial venules (HEV) via binding to specific carbohydrate structures on selectin ligands. Previous studies using sialidase treatment suggested a role of sialic acid residues in L‐selectin‐dependent rolling. To investigate the role of the α2,3‐sialyltransferase (ST3Gal)‐IV on L‐selectin ligand activity in vivo, we studied leukocyte rolling in inflamed venules of the cremaster muscle and in Peyer's patch HEV of ST3Gal‐IV‐deficient mice and littermate control mice. In cremaster muscle venules with or without TNF‐α treatment, L‐selectin‐dependent rolling was almost completely abolished in ST3Gal‐IV–/– mice. In both models, L‐selectin interacts with P‐selectin glycoprotein ligand‐1 (PSGL‐1) presented by adherent leukocytes and leukocyte fragments, but not with endothelial L‐selectin ligands. In contrast, L‐selectin‐dependent rolling in Peyer's patch HEV, which is mediated by unknown endothelial L‐selectin ligands, was not impaired in the absence of ST3Gal‐IV. Our in vivo data show that PSGL‐1, the molecule responsible for L‐selectin‐mediated leukocyte interactions in inflammation, is dependent on ST3Gal‐IV, while α2,3‐sialylation by ST3Gal‐IV is not necessary for L‐selectin ligand activity on high endothelial cells of Peyer's patch HEV.

It was the aim of the present study to get insight into some of the intracellular mechanisms by which the vasoconstrictor hormones angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine (NE) inhibit renin release from renal juxtaglomerular cells. To this end a primary cell culture from rat renal cortex was established that consisted of 50% juxtaglomerular cells. The cultured juxtaglomerular cells contained prominent renin granules closely resembling those in the intact kidney and responded to a number of stimuli of renin release. By using these cultures, we found that ANG II (10(-7) M), AVP (10(-6) M), and NE (10(-5) M) inhibited renin release and increased the calcium permeability of the plasma membrane of the cultured cells. Both the effects on renin release and on calcium permeability could be diminished or even be abolished by the calcium channel blocker verapamil (Vp) (10(-5) M). ANG II, AVP, and NE led to an increased formation of diacylglycerol (DAG), a well-known stimulator of protein kinase C (PKC). Moreover, a direct stimulation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) (10(-8)-10(-6) M) also inhibited renin release and increased the calcium permeability of the cell membrane. Similar to ANG II, AVP, and NE, the effects of TPA on calcium permeability and renin release could be diminished by Vp. In conclusion, these results point toward a common mechanism by which vasoconstrictors inhibit renin release from renal juxtaglomerular cells: ANG II, AVP, and NE activate a phospholipase C, which generates DAG.(ABSTRACT TRUNCATED AT 250 WORDS)

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Vasomotor responses (VMR) induced by local electrical stimulation were studied in the vasculature of the split hydronephrotic rat kidney by in vivo microscopy. Unipolar pulses, which were applied by a micropipette positioned close to the vessel wall, elicited local and propagated VMR. Depolarizing and hyperpolarizing currents caused vaso‐constriction and vasodilatation, respectively. The magnitude of VMR could be controlled within seconds by variation of pulse frequency, pulse width and voltage. VMR were abolished by slight retraction of the stimulating micro‐pipette. Repetitive electrical stimulation resulted in reproducibly uniform VMR. Propagated VMR decayed with increasing distance from the stimulation site. They decayed more rapidly in the upstream than in the downstream flow direction in interlobular arteries. The longitudinal decay was well approximated by an exponential function with significantly different length constants of 150 ± 40 μm (upstream, n= 5) and 420 ± 90 μm (downstream, n=8). Our results show that vasomotor responses, which are initiated by changes in membrane potential, are propagated over distances of potential physiological importance in interlobular arteries.