Vascular Na+/Ca2+ exchanger: implications for the pathogenesis and therapy of salt-dependent hypertension.

Abstract

The Na+/Ca2+ exchanger is an ion transporter that exchanges Na+ and Ca2+ in either Ca2+ efflux or Ca2+ influx mode, depending on membrane potential and transmembrane ion gradients. In arterial smooth muscle cells, the Na+/Ca2+ exchanger is thought to participate in the maintenance of vascular tone by regulating cytosolic Ca2+ concentration. Recent pharmacological and genetic engineering studies have revealed that the Ca2+ influx mode of vascular Na+/Ca2+ exchanger type-1 (NCX1) is involved in the pathogenesis of salt-dependent hypertension. SEA0400, a specific Na+/Ca2+ exchange inhibitor that preferentially blocks the Ca2+ influx mode, lowers arterial blood pressure in salt-dependent hypertensive models, but not in normotensive rats or other types of hypertensive rats. Furthermore, heterozygous mice with reduced expression of NCX1 are resistant to development of salt-dependent hypertension, whereas transgenic mice with vascular smooth muscle-specific overexpression of NCX1 readily develop hypertension after high-salt loading. SEA0400 reverses the cytosolic Ca2+ elevation and vasoconstriction induced by nanomolar ouabain, as well as humoral factors in salt-loaded animals. One possibility is that circulating endogenous cardiotonic steroids may be necessary for NCX1-mediated hypertension. These findings help to explain how arterial smooth muscle cells in blood vessels contribute to salt-elicited blood pressure elevation and suggest that NCX1 inhibitors might be therapeutically useful for salt-dependent hypertension.

• Authors: Takahiro Iwamoto
• Journal: American journal of physiology. Regulatory, integrative and comparative physiology (Am J Physiol Regul Integr Comp Physiol) Vol. 290 Issue 3 Pg. R536-45 (Mar 2006) ISSN: 0363-6119 [Print] United States
• PMID: 16467501 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antihypertensive Agents
• Sodium Chloride, Dietary
• Sodium-Potassium-Exchanging ATPase

Topics

• Animals
• Antihypertensive Agents (administration & dosage)
• Humans
• Hypertension (drug therapy, etiology, metabolism)
• Muscle, Smooth, Vascular (drug effects, physiopathology)
• Sodium Chloride, Dietary (adverse effects, metabolism)
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors, metabolism)