Tissue-specific gene expression in rat hearts and aortas in a model of vascular nitrate tolerance

Tamás Csont, Zsolt Murlasits, Dalma Ménesi, János Z. Kelemen, Péter Bencsik, Márton Pipicz, Veronika Fekete, Ágnes Zvara, László G. Puskás, Péter Ferdinandy

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7 Citations (Scopus)

Abstract

Nitroglycerin exerts a direct myocardial anti-ischemic effect even in the state of vascular nitrate tolerance. To examine the potentially diverse molecular responses in vascular and cardiac tissues, we investigated the gene expression profile of the heart and the aorta by DNA microarray in male Wistar rats that were previously made tolerant to the vascular effects of nitroglycerin. The blood pressure-lowering effect of nitroglycerin (1-100 μ g/kg) was markedly attenuated in rats pretreated for 3 days with 3 × 100 mg/kg nitroglycerin. Nitric oxide content was significantly elevated in the heart but not in the aorta of nitrate-tolerant animals, which indicated tissue-specific differences in nitroglycerin bioconversion. Of 7742 genes analyzed by DNA microarray, we found that although the expression of 25 genes changed significantly in the heart (increased: Tas2r119, Map6, Cd59, Kcnh2, Kcnh3, Senp6, Mcpt1, Tshb, Haus1, Vipr1, Lrn3, Lifr; decreased: Ihh, Fgfr1, Cryge, Krt9, Agrn, C4bpb, Fcer1a, Csf3, Hsd17b11, Hsd11b2, Ctnnbl1, Prpg1, Hsf1), only 14 genes were altered in the aorta (increased: Tas2r119, Ihh, Rrad, Npm1, Snai1; decreased: Tubb2b, Usp15, Sema6c, Wfdc2, Rps21, Ramp2, Galr1, Atxn1, Lhx1) in vascular nitrate tolerance. Quantitative reverse transcription polymerase chain reaction analysis of genes related to oxidative/nitrative/nitrosative stress also showed differential expression pattern in the heart and aorta. This is the first pharmacogenomic analysis showing that nitroglycerin treatment leading to vascular nitrate tolerance differentially impacts gene expression in vascular and cardiac tissues, which indicates different tissue-specific downstream signaling pathways.

Original languageEnglish
Pages (from-to)485-493
Number of pages9
JournalJournal of cardiovascular pharmacology
Volume65
Issue number5
DOIs
Publication statusPublished - May 26 2015

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Keywords

  • NOX
  • NOX4
  • SOD
  • heat shock
  • matrix metalloproteinase

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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