Microspheres were used in earlier studies to determine the distribution of blood flow within the intestinal wall, but the selection of microsphere size was not systematic. In one study, a 5-micrometers difference in mean diameter markedly altered the submucosal vs. mucosal distribution of microspheres. Therefore, we examined the effect of size on microsphere distribution within the gut wall. Loops of canine small bowel were perfused at constant pressure, and microspheres were injected in the following order: 9 +/- 1, 15 +/- 1, and 26 +/- 2 micrometers. Gut segments were separated into mucosal, submucosal, and muscularis tissues. The microspheres were recovered from digested tissues and venous blood. The number and diameter of spheres in an aliquot of resuspended spheres were determined by digital image analysis. The ratio of mucosal to submucosal accumulation varied 60-fold for sphere diameters from 8 to 20 micrometers. The muscularis' share did not vary systematically with sphere size. Approximately 20% of spheres less than 11 micrometers reached venous blood, whereas few (less than 1%) of larger sizes did. We conclude: 1) sphere distribution within the gut wall is size dependent, 2) correction for microsphere shunting will be difficult, because the route taken by untrapped spheres is unknown, and 3) fractionating intramural flow among the three layers is not practical with commercially available spheres. However, under control conditions 15-micrometers spheres seem to distribute independently of size between muscularis and a lumped mucosal-submucosal compartment.
We have studied the acute and chronic effects of an ACE inhibitor (captopril) on platelet function and the renin-angiotensin system in patients with congestive heart failure. Plasma concentrations of angiotensin II fell significantly after a single dose of captopril (25 mg) and during long-term treatment with captopril (2 weeks, 75 mg/day). Plasma renin activity increased significantly after both the single and repeated doses. Captopril did not affect ADP-induced platelet aggregation or concentrations. It seems unlikely that circulating angiotensin II affects ADP-induced platelet aggregation in patients with congestive heart failure.
The objective was to study renal morphology and angiotensin converting enzyme (ACE) activity in an animal model of metabolic syndrome. C57Bl/6 male mice were given: 1) tap water 2) 24 h access to 10% fructose water or 3) 12 h access to fructose water (dark period) and water (light period) for 8 weeks. Regular chow was available ad libitum. Mice on 12 h fructose consumed more total fructose and gained more weight than those with 24 h access. Upon conclusion of the dietary regimen, kidneys were collected for morphologic studies using PAS staining, immunohistochemical staining for ACE and ACE2 and ACE/ACE2 activity. ACE/ACE2 enzyme activity was measured using a mass spectrometric assay with endogenous peptide substrates. Immunohistochemical staining showed a stronger presence of ACE2 in the 12 h group over control and 24 h. ACE staining appeared unchanged. ACE2 activity in the 12 h group was 4 fold higher than in control and 24 h groups (C = 0.6±0.2, 24h = 0.6±0.08 vs. 12h = 2.5±0.4; p<0.05). ACE activity was not different between groups. Pathological changes were unremarkable except for mesangial expansion in the 12 h (C = 0.84±0.01, 24h = 0.88±0.01 vs. 12h = 0.92±0.009; p<0.05). Results document that the renal effects of fructose water are dependent on the timing and volume of consumption. Increased nocturnal fructose water intake is associated with elevated ACE2 activity without changes in ACE. Supported by NIH grant R01 HL09356
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