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Effects of diadenosine polyphosphates on glomerular volume.

ABSTRACT: 1. Diadenosine polyphosphates (P(1),P(3)-diadenosine triphosphate, Ap(3)A; P(1),P(4)-diadenosine tetraphosphate, Ap(4)A; and P(1),P(5)-diadenosine pentaphosphate, Ap(5)A) are vasoactive molecules. The experimental model of isolated rat renal glomeruli was used to investigate their effects on glomerular vasculature. We measured the changes of glomerular inulin space (GIS) as a marker of glomeruli contractility. 2. Ap(4)A and Ap(5)A induced concentration- and time-dependent reduction of GIS whereas Ap(3)A had no effect. The effects of Ap(4)A and Ap(5)A (both at 1 microM) were prevented by a nonselective P2 receptor antagonist, that is, suramin (10 microM) and P2Y receptor antagonist - reactive blue 2 (50 microM). However, the antagonist of P1 receptor, that is, theophylline (1 microM) and A(1) receptor 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 10 microM) did not affect the responses of glomeruli to Ap(4)A or Ap(5)A. 3. Ap(3)A, in contrast to Ap(4)A and Ap(5)A, prevented angiotensin II-induced reduction of GIS in a concentration- and time-dependent manner. This effect was partially prevented by suramin and markedly reduced by reactive blue 2 and the specific antagonist of P2Y(1) receptor - MRS 2179 (10 microM). However, theophylline and the specific antagonist of A(2) receptor - 3,7-dimethyl-1-propargylxanthine (DMPX; 10 microM) - did not affect Ap(3)A action. 4. We indicate that diadenosine polyphosphates changed the glomerular volume via activation of P2 receptors. We suggest that extracellular Ap(4)A and Ap(5)A via P2X and P2Y receptors may decrease and Ap(3)A via, at least in part, P2Y(1) receptors may increase filtration surface, which in turn may modify glomerular filtration rate.

SUBMITTER: Szczepanska-Konkel M

PROVIDER: S-EPMC1576094 | biostudies-other | 2005 Apr

REPOSITORIES: biostudies-other

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Project description:BackgroundAge, CKD risk factors, and kidney function are associated with larger glomerular volume and a higher percentage of globally sclerotic glomeruli. Knowledge of how these associations may differ by cortical depth is limited.MethodsTo investigate glomerular volume and glomerulosclerosis across different depths of cortex, we studied wedge sections of the renal parenchyma from 812 patients who underwent a radical nephrectomy (for a tumor), separately characterizing glomeruli in the superficial (subcapsular), middle, and deep (juxtamedullary) regions. We compared the association of mean nonsclerotic glomerular volume and of glomerulosclerosis (measured as the percentage of globally sclerotic glomeruli) with age, obesity, diabetes, smoking, kidney function, and structural pathology in the superficial, middle, and deep regions.ResultsThe superficial, middle, and deep regions showed significant differences in glomerular volume (0.0025, 0.0031, and 0.0028 µm3, respectively) and in glomerulosclerosis (18%, 7%, and 11%, respectively). There was a marked increase in glomerulosclerosis with age in the superficial region, but larger glomerular volume was not associated with age at any cortical depth. Glomerulosclerosis associated more strongly with arteriosclerosis and ischemic-appearing glomeruli in the superficial region. Hypertension, lower eGFR, and interstitial fibrosis associated with glomerulosclerosis and glomerular volume to a similar extent at any depth. Diabetes and proteinuria more strongly associated with glomerulosclerosis in the deep and middle regions, respectively, but neither associated with glomerular volume differently by depth. Obesity associated more strongly with glomerular volume in the superficial cortex.ConclusionsMost clinical characteristic show similar associations with glomerulosclerosis and glomerulomegaly at different cortical depths. Exceptions include age-related glomerulosclerosis, which appears to be an ischemic process and is more predominant in the superficial region.

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Effects of diadenosine polyphosphates on glomerular volume.

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