A variety of perturbations of calcium metabolism are reported to occur in the spontaneously hypertensive rat (SHR) compared to its genetic control the Wistar-Kyoto rat (WKY), including significant dysfunction of calcium handling by the proximal renal tubule of the SHR, resulting in impaired active calcium transport in the gut and an apparent renal calcium leak. We explored the intestinal and renal epithelia of 12- to 14-week-old SHR and WKY using electron microscopy. Biochemical comparisons of these transport epithelia included measurements of three vitamin D dependent cellular proteins and one structural protein: alkaline phosphatase, intestinal CaBP9K, renal CaBP28K, and villin expression. Electron microscopy demonstrated a patchy loss in microvilli in the SHR, accounting for approximately 10 to 15% of the total microvillar surface. In the kidney, morphological abnormalities were observed only in the proximal renal tubule. Again, there was patchy loss of microvilli from the brush border membrane. In SHR duodenal alkaline phosphatase activity was significantly reduced compared to the WKY (0.145 +/- 0.002 v 0.186 +/- 0.002 integrated extinction/min/micron 3 X 10(3) brush border (P less than .001). Duodenal CaBP9K and renal CaBP28K were significantly reduced in SHR compared to WKY. There were no differences in villin expression. These data are consistent with the previously characterized disturbances of active calcium transport in the intestine and inappropriate renal calcium leak in the SHR. While a possible link between these disturbances and hypertension remains to be determined, this study provides supportive evidence for a primary disturbance in cell calcium handling and transporting epithelia in this form of genetic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
A microdensitometric method was employed to determine enzyme activities in situ in undisrupted tissue rat duodenum. The effect of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] on glucose-6-phosphate dehydrogenase (G6PD) activity and on the two utilization pathways of synthesized NADPH, H1 (mixed function oxidation) and H2 (biosynthesis), was studied. In normal animals, a crypt-to-villus gradient of G6PD activity and of both NADPH utilization pathways was observed. A high level of NADPH utilization occurred predominantly via the H2 pathway. In vitamin D-deficient rat animals, G6PD activity in the middle part of the villus was approximately 60% lower than in normal animals [10.05 +/- 0.35 vs. 3.95 +/- 0.26 (means +/- SE) A585.min-1.micron-3 X 10(5), P less than 0.001] with reduced NADPH utilization via the H2 pathway (8.39 +/- 0.49 vs. 2.73 +/- 0.43 A585.min-1.micron-3 X 10(5), P less than 0.001) but not the H1 pathway (1.65 +/- 0.17 vs. 1.22 +/- 0.19 A585.min-1.micron-3 X 10(5), P = NS). Intraperitoneal administration of 1,25(OH)2D3 (500 pmol) to vitamin D-deficient animals resulted in increased G6PD activity within 30 min (4.09 +/- 0.38 vs. 5.51 +/- 0.39 A585.min-1.micron-3 X 10(5), P less than 0.05), attaining normal levels within 2 h. The H2 but not the H1 pathway of NADPH utilization increased significantly in response to 1,25(OH)2D3. This increase is essentially located in the basal and middle parts of the villus. Thus 1,25(OH)2D3 may influence biosynthesis in the duodenum via stimulation of G6PD activity and the H2 pathway of NADPH utilization.
Introduction Individuals who travel to high altitude experience variable levels of poor sleep quality and sleep disordered breathing, which can have neurocognitive and other systemic impacts. Past studies by our group and others have shown that the apnea hypopnea index (AHI) increases, and nocturnal oxygen saturation decreases at higher altitude. This may change over time with acclimatization to environmental hypoxemia. The aim of this study was to examine the trajectory and variability in high altitude sleep disordered breathing effects in healthy young adult volunteers. Methods Twenty healthy volunteers were recruited from a local university (35% women), mean age 23.5(20.0, 32.2) years and BMI of 30.0(28.0, 35.9) kg/m2. Peripheral Arterial tonometry based home sleep apnea tests (HSAT; WatchPat One) was performed on all subjects at sea level up to three days prior to transportation via car to high altitude (3800m White Mountain Research Center - Barcroft Station, CA). Participants continued HSAT testing for three consecutive nights at high altitude sleeping in any position, without oxygen, acetazolamide, or use of any other medications impacting sleep or breathing. Mixed effects modeling was used to compare sleep parameters across nights. Results Subjects' characteristics: median (IQR)[range] age 23(20,32)[19,39] years, BMI 30(28, 36)[23,48] kg/m2, 35% women. AHI at altitude night 1 (67±4 events/hour) was significantly higher than sea level (7±4 events/hour; P< 0.001). Mean sleep SpO2 at altitude night 1 (79±1%) was significantly lower than sea level (95±1%; P< 0.0001). There was no statistically significant change in AHI or mean sleep SpO2 on nights 1-3; however substantial variability was noted between individual trajectories. Conclusion Healthy young adults exhibit severe Sleep Disordered Breathing when traveling to high altitude. Despite acclimatization, the severity of Sleep Disordered Breathing remained relatively unchanged overall. However substantial differences in individual trajectories were apparent. Larger studies are needed to understand how differences in genetics, sex, and other factors might impact Sleep Disordered Breathing at altitude. In addition, the impacts of (or tolerances to) altitude are likely to be broadly informative towards Sleep Disordered Breathing, hypoxemia, and other areas. Support (if any) N/A
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