Conditional knockout of smooth muscle sodium calcium exchanger type-1 lowers blood pressure and attenuates angiotensin II-salt hypertension

Youhua Wang, Ling Chen, Meng Li, Helen Cha, Takahiro Iwamoto, Jin Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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 CreloxP 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 Ca2+ 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 a-adrenergic receptor activation.

Original languageEnglish (US)
Article numbere12273
JournalPhysiological reports
Volume3
Issue number1
DOIs
StatePublished - 2015

Funding

This study was supported by a National Heart, Lung and Blood Institute research grant R01-107654.

Keywords

  • Angiotension II-salt
  • Blood pressure
  • Myogenic response
  • Phenylephrine
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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