Topics on the Na+/Ca2+ exchanger: role of vascular NCX1 in salt-dependent hypertension.

Abstract

Excess salt intake is a major risk factor for hypertension. However, the molecular mechanisms underlying salt-dependent hypertension remain obscure. Our recent studies using selective Na(+)/Ca(2+) exchange inhibitors and genetically engineered mice provide compelling evidence that salt-dependent hypertension is triggered by Ca(2+) entry through Na(+)/Ca(2+) exchanger type 1 (NCX1) in arterial smooth muscle. Endogenous cardiac glycosides, which may contribute to salt-dependent hypertension, seem to be necessary for NCX1-mediated hypertension. Intriguingly, recent studies by Dostanic-Larson et al. using knock-in mice with modified cardiac glycoside binding affinity of Na(+),K(+)-ATPases demonstrate that this binding site plays an important physiological role in blood pressure control. Thus, when cardiac glycosides inhibit Na(+),K(+)-ATPase in arterial smooth muscle cells, the elevation of local Na(+) on the submembrane area is believed to facilitate Ca(2+) entry through NCX1, resulting in vasoconstriction. This proposed pathway may have enabled us to explain how to link dietary salt to hypertension.

• Authors: Takahiro Iwamoto, Satomi Kita
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 102 Issue 1 Pg. 32-6 (Sep 2006) ISSN: 1347-8613 [Print] Japan
• PMID: 16960423 (Publication Type: Journal Article, Review)

Chemical References

• Antihypertensive Agents
• Cardiac Glycosides
• Sodium Chloride, Dietary
• Sodium-Calcium Exchanger
• sodium-calcium exchanger 1
• Sodium Chloride
• Calcium

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Calcium (metabolism)
• Cardiac Glycosides (pharmacology)
• Humans
• Hypertension (chemically induced, physiopathology)
• Sodium Chloride
• Sodium Chloride, Dietary (pharmacology)
• Sodium-Calcium Exchanger (antagonists & inhibitors, physiology)
• Vasoconstriction (drug effects)