Endothelium-dependent vascular relaxation is defective in mice lacking (SARCO)endoplasmic reticulum CA2+ ATPase isoform 3 (SERCA3)

L. H. Liu, R. L. Sutliff, R. J. Paul, J. N. Lorenz, M. L. Miller, J. J. Duffy, T. Doetschman, G. E. Shull

Research output: Contribution to journalArticle

Abstract

SERCA3, an intracellular Ca2+ sequestering ATPase, is expressed in vascular endothelium and may therefore play a role in regulation of vascular tone. SERCAS-deficient mice have been generated by gene targeting. Homozygous null mutants (-/-) are born in expected numbers, grow to normal size, are fertile, and display no overt anatomical or behaviorial abnormalities. Freshly dissected segments of thoracic aorta were suspended in isolated organ baths for isometric force measurements. Concentration-dependent responses to KCl or phenylephrine (PE) were similar in wildtype and SERCA3 mutant groups, both with and without intact endothelium. Aortas were precontracted with PE (1uM) and exposed to acetylcholine (3nM to 1uM) to induce endothelium-dependent relaxation Maximum relaxation (as % initial contraction) was 65.5 ± 5.6 in wildtype and 34.3 ± 7.8 in SERCA3 mutant aorta (n =8); relaxations induced by the nitric oxide donor, sodium nitroprusside (0.1 to 10 nM) were similar in wildtype and mutants. These results suggest that ablation of SERCA3 did not affect smooth muscle contractility but altered a critical component of the signaling pathways that mediate endothelium-dependent relaxation of vascular smooth muscle.

Original languageEnglish (US)
Pages (from-to)A519
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Liu, L. H., Sutliff, R. L., Paul, R. J., Lorenz, J. N., Miller, M. L., Duffy, J. J., Doetschman, T., & Shull, G. E. (1997). Endothelium-dependent vascular relaxation is defective in mice lacking (SARCO)endoplasmic reticulum CA2+ ATPase isoform 3 (SERCA3). FASEB Journal, 11(3), A519.