New Insights into the Contribution of Arterial NCX to the Regulation of Myogenic Tone and Blood Pressure

被引:15
作者
Zhang, Jin [1 ]
机构
[1] Univ Maryland, Dept Physiol, Sch Med, Baltimore, MD 21201 USA
来源
SODIUM CALCIUM EXCHANGE: A GROWING SPECTRUM OF PATHOPHYSIOLOGICAL IMPLICATIONS | 2013年 / 961卷
关键词
Vascular smooth muscle; NCX1; knockdown; overexpression; Calcium; Myogenic tone; Vasoconstriction; Blood pressure; Membrane potential; TRPC; SEA0400; SMOOTH-MUSCLE-CELLS; RECEPTOR POTENTIAL CHANNELS; TISSUE-SPECIFIC EXPRESSION; MEDIATED CA2+ ENTRY; NA+-K+-ATPASE; NA+/CA2+ EXCHANGER; NA+-CA2+ EXCHANGER; SIGNALING MECHANISMS; CYTOSOLIC CA2+; UP-REGULATION;
D O I
10.1007/978-1-4614-4756-6_28
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Plasma membrane protein Na+/Ca2+ exchanger (NCX) in vascular smooth muscle (VSM) cells plays an important role in intracellular Ca2+ homeostasis, Ca2+ signaling, and arterial contractility. Recent evidence in intact animals reveals that VSM NCX type 1 (NCX1) is importantly involved in the control of arterial blood pressure (BP) in the normal state and in hypertension. Increased expression of vascular NCX1 has been implicated in human primary pulmonary hypertension and several salt-dependent hypertensive animal models. Our aim is to determine the molecular and physiological mechanisms by which vascular NCX influences vasoconstriction and BP normally and in salt-dependent hypertension. Here, we describe the relative contribution of VSM NCX1 to Ca2+ signaling and arterial contraction, including recent data from transgenic mice (NCX1 smTg/Tg, overexpressors; NCX1(sm-/-), knockouts) that has begun to elucidate the specific contributions of NCX to BP regulation. Arterial contraction and BP correlate with the level of NCX1 expression in smooth muscle: NCX1(sm-/-) mice have decreased arterial myogenic tone (MT), vasoconstriction, and low BP. NCX1(smTg/Tg) mice have high BP and are more sensitive to salt; their arteries exhibit upregulated transient receptor potential canonical channel 6 (TRPC6) protein, increased MT, and vasoconstriction. These observations suggest that NCX is a key component of certain distinct signaling pathways that activate VSM contraction in response to stretch (i.e., myogenic response) and to activation of certain G-protein-coupled receptors. Arterial NCX expression and mechanisms that control the local (sub-plasma membrane) Na+ gradient, including cation-selective receptor-operated channels containing TRPC6, regulate arterial Ca2+ and constriction, and thus BP.
引用
收藏
页码:329 / 343
页数:15
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