Alterations of store-operated calcium entry and cyclopiazonic acid-induced endothelium-derived relaxations in aging rat thoracic aorta

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ERAÇ Y. , SELLI C., Tosun M.

PHYSIOLOGY INTERNATIONAL, cilt.103, ss.146-156, 2016 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 103 Konu: 2
  • Basım Tarihi: 2016
  • Doi Numarası: 10.1556/036.103.2016.2.2
  • Sayfa Sayıları: ss.146-156


The purpose of our study was to investigate whether endothelium-derived relaxations induced by store depletion are altered in aging rat thoracic aorta. Vascular responses were measured in aortic segments isolated from young (2-4 month) and old (20-24 month) male Sprague-Dawley rats. In phenylephrine-contracted intact tissues, receptor-mediated and receptor-independent endothelium-derived relaxations were induced by acetylcholine (ACh) and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) blocker cyclopiazonic acid (CPA), respectively. In addition, CPA-induced changes in intracellular calcium levels were monitored in fura-2-loaded endothelium-denuded tissues. Real-time quantitative reverse transcription polymerase chain reaction and western blot analysis were performed to determine the transient receptor potential canonical (TRPC) 4 mRNA and protein levels. Endothelial TRPC4 mRNA levels were apparently decreased in aging rats. Immunoblot analysis showed that TRPC4 protein levels significantly decreased in intact aorta from 20- to 24-month-old rats compared to that from 2- to 4-month-old rats. ACh- and CPA-induced endothelium-dependent relaxations decreased in old rat aorta without any change in direct vasodilation induced by sodium nitroprusside. Store-operated Ca2+ entry (SOCE) induced by CPA was significantly decreased, whereas sarcoplasmic reticulum Ca2+ release was unaffected in endothelium-denuded aging rat aorta. In conclusion, TRPC4 downregulation could be associated with decreased endothelium-dependent vasorelaxations. As endothelial nitric oxide synthase is activated by SOCE-induced caveolar internalization, tracking the expression levels of SERCA, ion channels, and/or associated proteins involved in SOCE would lead to the development of novel therapeutics for age-related vasospastic disorders with dysfunctional endothelium.