Oxidized low density lipoprotein (OX-LDL) induced arterial muscle contraction signaling mechanisms

C. Subah Packer, Ami E. Rice, Tomalyn C. Johnson, Nancy J. Pelaez, Constance J. Temm, George V. Potter, William A. White, Alan H. Roth, Jesus H. Dominguez, Richard G. Peterson

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Oxidized low-density lipoprotein cholesterol (OX-LDL), a reactive oxidant, forms when reactive oxygen species interact with LDL. Elevated OX-LDL may contribute to high blood pressure associated with diseases such as diabetes and obesity. The current study objective was to determine if OX-LDL is a vasoconstrictor acting through the OX-LDL receptor (LOX1) on arterial smooth muscle and elucidate the intracellular signaling mechanism. Arteries were extracted from Sprague-Dawley rats (SD) and obese F<inf>1</inf> offspring (ZS) of Zucker diabetic fatty rats (ZDF) x spontaneously hypertensive heart failure rats (SHHF). Pulmonary arterial and aortic rings and caudal arterial helical strips were attached to force transducers in muscle baths. Arterial preparations were contracted with high KCl to establish maximum force development in response to membrane depolarization (P<inf>o</inf>). Addition of OX-LDL caused contractions of varying strength dependent on the arterial type. OX-LDL contractions were normalized to % P<inf>o</inf>. Caudal artery was more reactive to OX-LDL than aorta or pulmonary artery. Interestingly, LOX1 density varied with arterial type in proportion to the magnitude of the contractile response to OX-LDL. OX-LDL contractions in the absence of calcium generated about 50% as much force as in normal calcium. Experiments with myosin light chain kinase and Rho kinase inhibitors, ML-9 and Y-27632, suggest OX-LDL induced contraction is mediated by additive effects of two distinct signaling pathways activated concomitantly in the presence of calcium. Results may impact development of new therapeutic agents to control hypertension associated with disorders in which circulating LDL levels are high in a high oxidizing environment.

Original languageEnglish (US)
Pages (from-to)20-26
Number of pages7
JournalOpen Hypertension Journal
Volume6
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Arterial smooth muscle
  • Calcium-independent contraction
  • Diabetes
  • Hypertension
  • Oxidized-LDL
  • Vasoactive oxidants

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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