Increased brush-border membrane calcium transport in the intestine, but not the kidney tubule, of spontaneously hypertensive rats.

Since we and others have found a decrease in intestinal Ca2+ absorption and renal Ca2+ reabsorption in the mature spontaneously hypertensive rat (SHR) at the tissue and cell level, we asked whether the transport defect was located at the luminal or the basolateral side of the epithelial cell. We studied intestinal and renal Ca2+ transport using isolated epithelial brush-border membrane vesicles (BBMVs) in order to examine the luminal side of this transport. For technical reasons, the preparation of intestinal BBMVs was performed using a centrifugation technique, but for renal BBMVs a precipitation method was used. The vesicles obtained with these two different techniques had markedly different aspects by electron microscopy analysis. However, no morphological difference was apparent between the two rat strains for BBMVs of either preparation. SHR and normotensive control Wistar-Kyoto (WKY) rats were studied at the age of 5 and between 12 and 14 weeks, receiving a normal Ca (1%) and P (0.46%) diet. In 5 week old SHR, duodenal BBMV Ca2+ uptake kinetics were similar to that of WKY of same age. However, in 12 week old rats mean (+/- SD) Vmax of duodenal Ca2+ uptake was significantly enhanced in SHR compared with WKY (0.59 +/- 0.21 v 0.38 +/- 0.09 nmol/mg protein and 10 s, P < .01), whereas Km was similar in the two strains. By contrast, no difference was found for Vmax or Km of Ca2+ uptake in renal BBMVs in 12 week old rats. In conclusion, Ca2+ uptake was either enhanced (duodenum) or normal (kidney tubule) in the mature SHR, compared with the WKY of same age.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium uptake into enterocyte brush-border membrane vesicles is greater in spontaneously hypertensive than in normotensive control rats.

Arterial hypertension in the SHR is associated with disturbances of calcium homeostasis, compared with its normotensive control, the WKY. In order to study intestinal Ca2+ handling at the subcellular level, we examined 45Ca2+ uptake kinetics in isolated brush-border membrane vesicles (BBMV). Experiments were conducted in male, 12- to 14-week-old rats on a 1% Ca diet. BBMV were purified by the method of Forstner et al. No difference in BBMV enrichment was observed between SHR and WKY. Ca2+ uptake was studied at various Ca2+ concentrations in the incubation medium (0.025-1.0 mM) and could be separated into a nonsaturable and a saturable component. The saturable component followed Michaelis-Menten kinetics. Vmax in the SHR was greater than in the WKY: 0.576 +/- 0.186 (n = 6) vs. 0.346 +/- 0.10 nmol/mg protein x 10 s (n = 6), mean +/- SD, p less than 0.05. However, Km was not different in the two animal strains. In conclusion, mediated Ca2+ transport into duodenal BBMV was increased in the adolescent SHR. When considering that the transcellular duodenal Ca2+ flux is decreased in the SHR at this age, the rate-limiting step of perturbed transeptithelial Ca2+ transport is probably localized at the site of the basolateral membrane.

Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat.

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)

Calcium uptake kinetics into brush-border membrane vesicles: higher Vmax in the spontaneously hypertensive rat than in normotensive control.

Arterial hypertension in the spontaneously hypertensive rat (SHR) is associated with an abnormal Ca2+ homeostasis, compared with its normotensive control, the Wistar Kyoto rat (WKY). In particular, epithelial Ca2+ transport is perturbed, with intestinal absorption and renal tubular reabsorption being decreased in the adolescent and adult SHR. In the present study we examined Ca2+ uptake into isolated duodenal brush-border membrane vesicles (BBMV) in 12-14 week-old male rats. This uptake can be separated in a nonsaturable and a saturable component. The latter follows Michaelis-Menten kinetics. Vmax of this component was found to be significantly higher (p less than 0.05) in SHR than in WKY (0.58 +/- 0.19 versus 0.35 +/- 0.06 nmol/mg protein x 10 sec, mean +/- SD) whereas Km did not differ. Thus, the defect in the intestinal Ca2+ absorption previously identified in the SHR of this age is not due to a decrease in Ca uptake at the level of the duodenal brush-border membrane, but is most likely located in the baso-lateral membrane.

Ultrastructural and functional abnormalities of intestinal and renal epithelium in the SHR.

Intestinal calcium transport, renal tubular calcium reabsorption, and plasma 1.25 (OH)2 vitamin D3 (calcitriol) levels have all been reported to be diminished in the spontaneously hypertensive rat (SHR) compared with its genetic control the Wistar Kyoto rat (WKY). In the present study, absorptive duodenal and renal tubular epithelia of 12- to 14-week-old male SHR and WKY were examined by electron microscopy to determine whether such disturbances could be related to structural abnormalities. Patchy loss of microvilli in both duodenal and proximal tubular epithelia was observed in the SHR, whereas brush border membrane was entirely normal in the WKY. Irregular spaces were observed between the basal aspects of SHR intestinal epithelial cells and their basement membrane. In addition, the average height of duodenal and renal microvilli was reduced in the SHR. Two specific markers of the brush border membrane, alkaline phosphatase and villin, as well as the cytoplasmic vitamin-D dependent calcium-binding proteins, CaBP9K and CaBP28K were determined. Duodenal alkaline phosphatase activity was reduced in the SHR, compared with the WKY: 0.145 +/- 0.002 vs. 0.186 +/- 0.002 IE/min.microns 3 x 10(3) brush border, mean +/- SEM, N = 10 pairs, P less than 0.001. However, duodenal villin expression was not different from that of the WKY. Duodenal CaBP9K and renal CaBP28K content was diminished in the SHR: 21.0 +/- 0.80 vs. 29.9 +/- 2.19 micrograms/mg protein, N = 6 pairs, P less than 0.01 for duodenum, and 4.47 +/- 0.39 vs. 7.67 +/- 0.54 micrograms/mg protein, N = 6 pairs, P less than 0.001 for kidney. These data showing structural and functional abnormalities of intestinal and kidney cells in the SHR appear to reflect a disorder of transporting epithelia which may be either intrinsic or related to reduced circulating calcitriol.

General toxicity of water-soluble iodinated contrast media. Pathogenic concepts.

Despite many studies, the mechanism of the general accidents induced by the intravascular injection of water-soluble iodinated contrast media remains unclear. Two theories are proposed; until now, they have not been related to each other. Lalli emphasizes the role of a cerebral impact related to stress, which induces a chain of accidents that are perhaps more aggressive when the molecules cross the blood-brain barrier. Lasser has proposed a theory based on the biochemical catastrophies secondary to the damage of the vascular endothelium and the activation of the Hageman's factor XII. A true anaphylaxis has not been proven: specific immunoglobulins are only exceptionally found, and an actual primary activation of the complement system pathway with mediator release is a controversial phenomenon in vivo. The anaphylactoid collapses result from a chemotoxic effect that might be decreased by several kinds of pharmaceutical premedications; none of them are constantly efficient. The new low osmolar molecules have a very low general toxicity, but their use does not guarantee the lack of anaphylactoid reactions.

Prodromal itching in childhood asthma.

In a prospective study of 79 children with asthma, 26 had prodromal itching 1 - 30 min before the attack, and 17 had prodromal itching during the early part of the attack. The sensation lasted up to about 30 min. Scratch marks were seen in 5 patients. In 7 patients the itching was known to the child but had not been recognised by the parents. The site of itching was constant for each patient, being the anterior part of the neck in 14 patients and the upper part of the back in 9 patients. The pathogenesis of prodromal itching is obscure, but its recognition may be of diagnostic use when taking a history and may enable an attack of asthma to be aborted or treated more promptly.