Disease relevance of Pgc

• BACKGROUND: Elevated glucose levels and glomerular hypertension (Pgc) are considered to contribute to the elaboration of matrix protein by mesangial cells (MCs) in diabetic glomeruli [1].
• Tight glucose control or reduction in Pgc clinically delays progression of diabetic nephropathy [1].
• In rats, severe diabetic nephropathy can occur without an increase in Pgc, while in humans, hyperfiltration does not appear to be a predictor of proteinuria and renal dysfunction [2].
• Infusion of adenosine, 0.05 mumol/min . kg body weight, into the thoracic aorta, was associated with a fall of directly measured glomerular capillary pressure (Pgc) from 45.2 + 1.8 to 32.5 + 1.7 mm Hg, P less than 0.001 [3].
• Enalapril-treated OZR had less albuminuria and lower blood pressure, but Pgc was not reduced [4].

High impact information on Pgc

• The present results suggested that the appearance of pyloric glands with a low Pg 1 content in normal-looking mucosa might be an immunohistochemically detectable preneoplastic change preceding morphologically detectable preneoplastic changes in stomach carcinogenesis [5].
• After MNNG treatment, tissues showing changes were classified into normal-looking pyloric mucosa with a low Pg 1 content, mucosa showing atrophic or hyperplastic changes, adenomatous hyperplasia, and adenocarcinoma [5].
• After MNNG treatment, class III mucin-positive pyloric glands with a low Pg 1 content in normal-looking pyloric mucosa were found from week 10; subsequently, their number increased with time [5].
• Almost all cells of the pyloric gland cell type (greater than 95%) in areas of adenomatous hyperplasia and adenocarcinomas had little or no Pg 1 content [5].
• From the results of paradoxical Con A staining and Pg 1 immunostaining, the cells in lesions were classified into gastric types (surface mucous cell type and pyloric gland cell type) and intestinal types (intestinal-absorptive cell type and goblet cell type) [5].

Chemical compound and disease context of Pgc

• Constant GFR and SFP1/2max under efonidipine suggest that single nephron GFR and Pgc remain unaltered and that a marked reduction in proteinuria is achieved without changes in single nephron GFR or Pgc of superficial nephrons [6].
• Northern blot analysis revealed that PGC gene expression was enhanced not only in acetic acid-induced chronic gastric ulcers but also in indomethacin-induced gastric mucosal lesions [7].

Biological context of Pgc

• The nucleotide sequences of the coding regions and the 5'- and 3'-flanking regions of one of the rat pepsinogen C genes have been determined [8].
• The entire rat pepsinogen C gene has been isolated from a rat genomic library, using the rat pepsinogen C cDNA as a probe [8].
• The 5'-flanking region is similar to that of the human pepsinogen C gene, but only the former has the core sequence of the Sp1 binding site [8].
• Again, CIn (4.22 ml X min-1 X kg-1 in PF vs. 2.69 in CA), RPF (16.1 ml X min-1 X kg-1 vs. 8.3), and Pgc (48 mm Hg vs. 38) were decreased, and renal vascular resistance (4.9 mm Hg/ml vs. 8.0) was increased [9].
• Inulin clearance, (CIn, 4.5 ml X min-1 X kg-1 per kidney pre vs. 1.3 post), renal plasma flow (RPF, 12.0 ml X min-1 X kg-1 vs. 7.4), and the estimated pressure in the glomerular capillaries (Pgc, 52 mm Hg vs. 40), were all significantly decreased while renal vascular resistance (5.2 mm Hg/ml vs. 12.0) was increased [9].

Anatomical context of Pgc

• Elevation of ureter pressure to 39 + 2 mm Hg abolished the fall of Pgc following adenosine infusion, 51.3 + 1.7 vs. 50.0 + 1.3 mm Hg, NS [3].
• Reduction of renal artery pressure to 70 mm Hg by an aortic clamp above the renal arteries also prevented the fall of Pgc due to adenosine, 36.8 + 0.9 vs. 36.4 + 1.8 mm Hg, NS [3].
• 3. Micropuncture experiments revealed that the maximal reduction of proximal stop-flow pressure (SFP), an index of glomerular capillary pressure (Pgc), induced by loop of Henle perfusion was significantly less with efonidipine treatment (6.7 +/- 1.0% of SFP with no loop flow) than in control (23.8 +/- 3.1%) [6].
• From these results, we suggest that MDP significantly decreases Pgc in the steady state not only by the reduction of RPP, but also by the amelioration of renal microcirculation [10].
• All pyloric glands of control rats in weeks 30 and 70 contained class III mucins and had a high Pg 1 content demonstrated immunohistochemically [5].

Associations of Pgc with chemical compounds

• The amount of transcripts of the rat pepsinogen C genes was found to increase during development, and a similar increase was shown to be induced by injection of hydrocortisone [8].
• In the presence of efonidipine, SFP at half-maximal reduction (SFP1/2max), which approximates Pgc at the in vivo steady state tubular flow rate, remained unchanged compared with control (36.9 +/- 0.8 vs 35.3 +/- 0.7 mmHg, respectively) and the slope of dependency on mean BP was not different between control and efonidipine [6].
• Central to the assumption that glomerular capillary pressure (Pgc) can be equated with the sum of arterial oncotic pressure (pi art) and the pressure in a blocked proximal tubule ("stop flow" pressure, Psf) is that filtration ceases in the blocked nephron [11].
• Through balanced systemic and glomerular vasodilatation, lemildipine maintains the levels of Pgc and GFR in the face of reduced renal perfusion pressure [12].
• Lacidipine partially prevented SNGFR (43.1 +/- 14.3 nL/min) and Kf decline (2.08 +/- 1.10 nl/min/mm Hg) despite the presence of elevated Pgc [13].

Other interactions of Pgc

• Because in vivo studies show that nitric oxide (NO) in the remnant kidney limits glomerular injury without reducing Pgc, we studied whether NO attenuated stretch-induced p38 activation in MC [14].
• The current investigation examines the changes in the expression of pepsinogen C and cathepsin D and E genes in the gastric mucosa during aging and following physiological stimuli of fasting and refeeding [15].

Analytical, diagnostic and therapeutic context of Pgc

• Southern blot analysis showed that there exists at least two rat pepsinogen C genes [8].
• Should filtration not cease, but continue at a rate equal to tubular reabsorption between the block and the glomerulus, Psf, for a given Pgc, will depend on the distance between block and glomerulus [11].
• On Northern blotting with a Pg1 complementary DNA probe, Pg1 mRNA was detected only in the glandular stomach of normal rats [16].
• Immunocytochemistry and in situ hybridization studies of pepsinogen C-producing cells in developing rat fundic glands [17].
• PGC expression was detected in the IEC-6 cells by RT-PCR and immunocytochemistry, using a PGC specific antibody, localised the protein to cytoplasmic secretory granules [18].

References