title: Conditional knockout of smooth muscle sodium calcium exchanger type-1 lowers blood pressure and attenuates Angiotensin II-salt hypertension.
abstract: The functions of smooth muscle sodium calcium exchanger (NCX) in the vasculature are controversial and poorly understood. To determine the possible roles of NCX in the vascular phenotype and function, we developed a novel mouse model (SM-NCX1 KO) in which the smooth muscle-specific NCX type-1 (NCX1) was conditionally knocked out using tamoxifen-inducible Cre-loxP recombination technique. SM-NCX1 KO mice exhibit significantly lower blood pressure and attenuated angiotensin II (Ang II)-salt-induced hypertension (measured by radio telemetry and intra-arterial catheterization). Isolated, pressurized mesenteric small resistance arteries from SM-NCX1 KO mice, compared to control arteries, were characterized by the following: (1) ~90% reduced NCX1 protein expression; (2) impaired functional responses to (i) acute NCX inhibition by SEA0400 or SN-6, (ii) NCX activation by low [Na(+)]o, and (iii) Na(+) pump inhibition by ouabain; (3) attenuated myogenic reactivity; and (4) attenuated vasoconstrictor response to phenylephrine but not Ang II. These results provided direct evidence that arterial NCX1 normally mediates net Ca(2+) influx that helps maintain basal vascular tone in small resistance arteries and blood pressure under physiological conditions. Importantly, NCX1 contributes to blood pressure elevation in Ang II-salt hypertension, possibly by regulating α-adrenergic receptor activation.
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Youhua
authors: Y
authors: Wang
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Ling
authors: L
authors: Chen
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Meng
authors: M
authors: Li
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Helen
authors: H
authors: Cha
authors: Department of Pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan.
authors: Takahiro
authors: T
authors: Iwamoto
authors: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors: Jin
authors: J
authors: Zhang
keywords: Angiotension II‐salt; blood pressure; myogenic response; phenylephrine; vascular smooth muscle
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