Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

So far, two isoforms of the neutral Na+K+-2Cl- cotransporter have been cloned in mammals. One isoform, BSC1, mediates apical ion entry in the renal thick ascending limb of Henle and a second, BSC2, appears to be an ubiquitously expressed Na+K+-2Cl- cotransporter. In primary cultures of rabbit proximal tubule, porcine aortic endothelial cells, and rat vascular smooth muscle cells, expression of the second isoform BSC2 was demonstrated by Northern blot analysis and bumetanide-sensitive 86Rb+ uptake studies. A surprising finding was the absence of BSC2 in fully differentiated freshly-isolated proximal tubule, porcine aortic endothelial cells, and rat vascular smooth muscle cells. Several studies have reported modulation of Na+K+-2Cl- cotransport activity by vasoactive substances and suggested a role for disturbed cotransport in, for example, the pathogenesis of essential hypertension. All these observations, however, were made in cultured cells which, in view of our findings, makes the physiological relevance questionable.
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PMID:Culturing induced expression of basolateral Na+-K+-2Cl- cotransporter BSC2 in proximal tubule, aortic endothelium, and vascular smooth muscle. 858 42

Prenatal factors, especially intrauterine growth retardation, have been shown to correlate with the risk of essential hypertension in adult life, but the mechanisms are unknown. An experimental model of prenatal programming of hypertension in the rat, induced by a maternal low-protein diet during pregnancy, was employed to study the role of renal Na reabsorption in the pathogenesis. The abundance of the apical Na transporter type III Na/H exchanger (NHE3), bumetanide-sensitive Na-K-2Cl cotransporter (BSC1), thiazide-sensitive Na-Cl cotransporter (TSC), and the amiloride-sensitive epithelial Na channel (ENaC) was determined by semiquantitative immunoblotting in kidneys from the offspring at 4 wk of age, before hypertension became manifest. There were no significant differences between the experimental and control rats in the abundance of NHE3 or any of the ENaC subunits. In contrast, the quantity of BSC1 in the experimental group was increased to 302% of control (P < 0.001) and that of TSC to 157% of control (P < 0.05). Determination of specific mRNA levels by ELISA-linked RT-PCR revealed a significantly increased BSC1 mRNA at 1 day (P < 0.01), 4 wk (P < 0.01), and 8 wk (P < 0.001) of age, and a significantly increased TSC mRNA at 4 wk of age (P < 0.05) in the experimental group. The results suggest that prenatal programming of hypertension involves transcriptional upregulation of Na transport in thick ascending limb and distal convoluted tubule.
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PMID:Upregulation of renal BSC1 and TSC in prenatally programmed hypertension. 1206 Jun 3

Renal sodium handling is an essential physiologic function in mammal for body fluid maintenance and blood pressure regulation. Recent advances in molecular biology have led to the identification of kidney-specific sodium transporters in the renal tubule, thereby supplying vast information for renal physiology as well as systemic physiology. Renal urinary concentration for body fluid maintenance is accomplished by counter current multiplication in the distal tubule. Sodium transport in the thick ascending limb of Henle (TAL) is the initial process of this system. We have demonstrated that renal urinary concentration is regulated in part by the expression of the Na(+)-K(+)-2Cl(-) co-transporter (BSC1) in TAL, by showing two mechanisms of BSC1 expression: pitressin vasopressin (AVP)-dependent and AVP-independent mechanisms. Two additional findings, namely, a lack of the ability to increase BSC1 expression leads to urinary concentrating defect and an enhanced BSC1 expression underlies the edema-forming condition, confirm the close association between sodium handling in TAL and body fluid accumulation. The lines of evidence from our genetic studies of the general Japanese population suggest the importance of mendelian hypertension genes in the genetic investigation of essential hypertension. Because those genes directly or indirectly regulate sodium transport by the Na-Cl co-transporter or the epithelial sodium channel in the distal convoluted tubule to the collecting duct (distal tubular segments after TAL), sodium handling in this part of the renal tubule may be, at least in part, involved in blood pressure regulation. The unveiling of such physiologic roles of sodium handling based on the sodium transporters or on the tubular segments may lead to a better understanding of systemic physiology as well as to the development of novel therapy for body fluid or blood pressure disorders.
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PMID:Renal sodium handling for body fluid maintenance and blood pressure regulation. 1517 65