Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Epithelial abnormalities in intestine and kidney of the spontaneously hypertensive rat. 222 67

This presentation has reviewed evidence from our laboratory that both structural and functional changes participate in the initiation and maintenance of hypertension in spontaneously hypertensive rats (SHR). Structural changes are present in the muscular arteries of the mesenteric and renal vasculature at 3- to 5-week-old SHR as compared with WKY. The major structural change in SHR arteries was increased cross-section area with increased thickness of the media owing to hyperplasia of smooth muscle; lumen sizes were interchanged. Later, at 10-12, 21, and 28 weeks of age, there was further increase in medial thickness owing to hyperplasia, and some hypertrophy and changes in elastic arteries also became evident. Increases in medial thickness of elastic arteries included hypertrophy as well as hyperplasia. Changes in lumen diameter were never observed in arteries fixed in a relaxed state at physiological flow rates. In addition, a deficit in Ca handling (decreased ATP-dependent Ca2+ accumulation) was observed in plasma-membrane vesicles from mesenteric arteries of SHR prior to and after the development of hypertension. It persisted when hypertension was reversed by hydralazine in SHR. It was present in various forms of experimental hypertension. It was present whenever hypertension was present and disappeared with normalization of blood pressure by withdrawal of the stimulus. The Ca-handling deficit was found in several nonarterial tissues and may be a generalized genetic defect in SHR. It was always accompanied by increased alkaline phosphatase activity of plasma membranes, and this was suggested to reflect the smooth-muscle hyperplasia occurring simultaneously. A model of the initiation and maintenance of hypertension based on medial thickening and deficient Ca handling as primary, interacting causes of genetic hypertension is proposed.
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PMID:Early structural changes in precapillary vessels in hypertension and their relationship to functional changes. 608 10

Microsomal fractions were isolated from the smooth muscle of gastric fundus, vasa deferentia and mesenteric arteries of rats made hypertensive by deoxycorticosterone-salt treatment. Several enzymatic activities, Ca2+ binding and ATP-dependent Ca2+ accumulation of the microsomal fractions from these hypertensive rats were compared with those from the control of rats which remained normotensive under similar treatment. Altered membrane properties were observed in microsomal fractions isolated from vascular smooth muscle but not in those isolated from non-vascular smooth muscles in this form of experimental hypertension. These alterations included decreased Mg2+ ATPase activity, enhanced alkaline phosphatase activity, decreased Ca2+ binding in the absence of ATP and decreased ATP-dependent Ca2+ accumulation. This result is in contrast to our previous findings that decreased ATP-dependent Ca2+ accumulation was observed in microsomal fraction isolated from non-vascular smooth muscles of rats with genetic hypertension. The present study, together with our previous findings, support the contention that altered Ca2+ handling by vascular smooth muscle is associated with the pathogenesis of hypertension, whereas altered Ca2+ handling by non-vascular smooth muscles previously observed in spontaneous hypertension may be associated with genetic factors not related to hypertension.
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PMID:Membrane abnormalities occur in vascular smooth muscle but not in non-vascular smooth muscle from rats with deoxycorticosterone-salt induced hypertension. 668 Oct 43