Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning

Effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress

Ioanna Andreadou, Dimitrios Farmakis, Eftihios Prokovas, Fragiska Sigala, Anastasia Zoga, Katerina Spyridaki, Apostolos Papalois, Andreas Papapetropoulos, Maria Anastasiou-Nana, Dimitrios Th Kremastinos, Efstathios K. Iliodromitis

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Aims The effectiveness of postconditioning (POC) in hypercholesterolaemia is in dispute. We investigated the effects of 3-day lipophilc (simvastatin) or hydrophilic (pravastatin) statin treatment, without or with POC in normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits. Methods and resultsNorm or Chol rabbits were subjected to 30 min ischaemia and randomized in two series of 12 groups each: control, simvastatin (Sim), pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol, Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low density lipoprotein plasma level evaluation; animals of the second series underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT), malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N-nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L-NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced infarction in Norm (24.3 ± 1.3, 25.9 ± 2.8, 27.9 ± 3.1, 23.3 ± 2.3, and 33.4 ± 2.5, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs. 49.3 ± 1.9 in control, P < 0.05), but only Prav did so in Chol animals (25.7 ± 3.3 and 25.3 ± 3.9 in Prav-Chol and Prav-POC-Chol vs. 50.9 ± 1.7, 44.8 ± 4.3, 41.5 ± 3.5, and 49.3 ± 5.5 in Chol, Sim-Chol, POC-Chol, and Sim-POC-Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the only intervention that increased myocardial eNOS and Akt in Chol rabbits (P < 0.05 vs. all others). Conclusion Prav, in contrast to same-dose Sim or POC, reduces infarction in Chol rabbits independently of lipid lowering, potentially through eNOS activation and nitro-oxidative stress attenuation.

Original languageEnglish (US)
Pages (from-to)501-509
Number of pages9
JournalCardiovascular research
Volume94
Issue number3
DOIs
StatePublished - Jun 1 2012
Externally publishedYes

Fingerprint

Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pravastatin
Nitric Oxide Synthase Type III
Simvastatin
Oxidative Stress
Rabbits
NG-Nitroarginine Methyl Ester
Infarction
Reperfusion
Ischemia
Dissent and Disputes
Hypercholesterolemia
Malondialdehyde
LDL Cholesterol

Keywords

  • Hypercholesterolaemia
  • Postconditioning
  • Pravastatin
  • Simvastatin
  • Statins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning : Effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress. / Andreadou, Ioanna; Farmakis, Dimitrios; Prokovas, Eftihios; Sigala, Fragiska; Zoga, Anastasia; Spyridaki, Katerina; Papalois, Apostolos; Papapetropoulos, Andreas; Anastasiou-Nana, Maria; Kremastinos, Dimitrios Th; Iliodromitis, Efstathios K.

In: Cardiovascular research, Vol. 94, No. 3, 01.06.2012, p. 501-509.

Research output: Contribution to journalArticle

Andreadou, I, Farmakis, D, Prokovas, E, Sigala, F, Zoga, A, Spyridaki, K, Papalois, A, Papapetropoulos, A, Anastasiou-Nana, M, Kremastinos, DT & Iliodromitis, EK 2012, 'Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning: Effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress', Cardiovascular research, vol. 94, no. 3, pp. 501-509. https://doi.org/10.1093/cvr/cvs121
Andreadou, Ioanna ; Farmakis, Dimitrios ; Prokovas, Eftihios ; Sigala, Fragiska ; Zoga, Anastasia ; Spyridaki, Katerina ; Papalois, Apostolos ; Papapetropoulos, Andreas ; Anastasiou-Nana, Maria ; Kremastinos, Dimitrios Th ; Iliodromitis, Efstathios K. / Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning : Effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress. In: Cardiovascular research. 2012 ; Vol. 94, No. 3. pp. 501-509.
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abstract = "Aims The effectiveness of postconditioning (POC) in hypercholesterolaemia is in dispute. We investigated the effects of 3-day lipophilc (simvastatin) or hydrophilic (pravastatin) statin treatment, without or with POC in normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits. Methods and resultsNorm or Chol rabbits were subjected to 30 min ischaemia and randomized in two series of 12 groups each: control, simvastatin (Sim), pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol, Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low density lipoprotein plasma level evaluation; animals of the second series underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT), malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N-nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L-NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced infarction in Norm (24.3 ± 1.3, 25.9 ± 2.8, 27.9 ± 3.1, 23.3 ± 2.3, and 33.4 ± 2.5, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs. 49.3 ± 1.9 in control, P < 0.05), but only Prav did so in Chol animals (25.7 ± 3.3 and 25.3 ± 3.9 in Prav-Chol and Prav-POC-Chol vs. 50.9 ± 1.7, 44.8 ± 4.3, 41.5 ± 3.5, and 49.3 ± 5.5 in Chol, Sim-Chol, POC-Chol, and Sim-POC-Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the only intervention that increased myocardial eNOS and Akt in Chol rabbits (P < 0.05 vs. all others). Conclusion Prav, in contrast to same-dose Sim or POC, reduces infarction in Chol rabbits independently of lipid lowering, potentially through eNOS activation and nitro-oxidative stress attenuation.",
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T1 - Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning

T2 - Effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress

AU - Andreadou, Ioanna

AU - Farmakis, Dimitrios

AU - Prokovas, Eftihios

AU - Sigala, Fragiska

AU - Zoga, Anastasia

AU - Spyridaki, Katerina

AU - Papalois, Apostolos

AU - Papapetropoulos, Andreas

AU - Anastasiou-Nana, Maria

AU - Kremastinos, Dimitrios Th

AU - Iliodromitis, Efstathios K.

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Aims The effectiveness of postconditioning (POC) in hypercholesterolaemia is in dispute. We investigated the effects of 3-day lipophilc (simvastatin) or hydrophilic (pravastatin) statin treatment, without or with POC in normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits. Methods and resultsNorm or Chol rabbits were subjected to 30 min ischaemia and randomized in two series of 12 groups each: control, simvastatin (Sim), pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol, Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low density lipoprotein plasma level evaluation; animals of the second series underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT), malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N-nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L-NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced infarction in Norm (24.3 ± 1.3, 25.9 ± 2.8, 27.9 ± 3.1, 23.3 ± 2.3, and 33.4 ± 2.5, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs. 49.3 ± 1.9 in control, P < 0.05), but only Prav did so in Chol animals (25.7 ± 3.3 and 25.3 ± 3.9 in Prav-Chol and Prav-POC-Chol vs. 50.9 ± 1.7, 44.8 ± 4.3, 41.5 ± 3.5, and 49.3 ± 5.5 in Chol, Sim-Chol, POC-Chol, and Sim-POC-Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the only intervention that increased myocardial eNOS and Akt in Chol rabbits (P < 0.05 vs. all others). Conclusion Prav, in contrast to same-dose Sim or POC, reduces infarction in Chol rabbits independently of lipid lowering, potentially through eNOS activation and nitro-oxidative stress attenuation.

AB - Aims The effectiveness of postconditioning (POC) in hypercholesterolaemia is in dispute. We investigated the effects of 3-day lipophilc (simvastatin) or hydrophilic (pravastatin) statin treatment, without or with POC in normocholesterolaemic (Norm) and hypercholesterolaemic (Chol) rabbits. Methods and resultsNorm or Chol rabbits were subjected to 30 min ischaemia and randomized in two series of 12 groups each: control, simvastatin (Sim), pravastatin (Prav), POC, Sim-POC, Prav-POC, Chol, Sim-Chol, Prav-Chol, POC-Chol, Sim-POC-Chol, Prav-POC-Chol. After ischaemia, rabbits of the first series underwent 3 h reperfusion, followed by infarct size, total cholesterol, and low density lipoprotein plasma level evaluation; animals of the second series underwent 10 min reperfusion followed by tissue sampling for nitrotyrosine (NT), malondialdehyde, endothelial nitric oxide synthase (eNOS), and Akt analyses. N-nitro-l-arginine methylester (L-NAME) was given in two additional groups (POC-L-NAME and Prav-Chol-L-NAME) for infarct size assessment. All interventions reduced infarction in Norm (24.3 ± 1.3, 25.9 ± 2.8, 27.9 ± 3.1, 23.3 ± 2.3, and 33.4 ± 2.5, in POC, Sim, Prav, Sim-POC, and Prav-POC groups, respectively, vs. 49.3 ± 1.9 in control, P < 0.05), but only Prav did so in Chol animals (25.7 ± 3.3 and 25.3 ± 3.9 in Prav-Chol and Prav-POC-Chol vs. 50.9 ± 1.7, 44.8 ± 4.3, 41.5 ± 3.5, and 49.3 ± 5.5 in Chol, Sim-Chol, POC-Chol, and Sim-POC-Chol, respectively, P < 0.05). L-NAME abolished the infarct size-limiting effect of POC and Prav-Chol. Prav induced the greatest reduction in NT, while it was the only intervention that increased myocardial eNOS and Akt in Chol rabbits (P < 0.05 vs. all others). Conclusion Prav, in contrast to same-dose Sim or POC, reduces infarction in Chol rabbits independently of lipid lowering, potentially through eNOS activation and nitro-oxidative stress attenuation.

KW - Hypercholesterolaemia

KW - Postconditioning

KW - Pravastatin

KW - Simvastatin

KW - Statins

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