Evidence for enhanced eNOS function in coronary microvessels during the second window of protection

Song Jung Kim, Xiaoping Zhang, Xiaobin Xu, Alice Chen, Joaquin B. Gonzalez, Sharat Koul, Kalpana Vijayan, George J. Crystal, Stephen Vatner, Thomas H. Hintze

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Nitric oxide (NO) derived from endothelial NO synthase (NOS) (eNOS) has been identified as a trigger for the second window of protection (SWOP), but its role as a mediator during the SWOP is a matter of debate. Eighteen mongrel dogs were chronically instrumented to measure left ventricular function, coronary blood flow, and wall thickening. Myocardial preconditioning was induced by 10 min coronary artery occlusion. After 24 h of reperfusion (during the SWOP), the hearts were excised. Coronary microvessels were isolated and incubated in presence of 1) the endothelium-dependent agonists carbachol and bradykinin, 2) the calcium ionophore A23187, and 3) the angiotensin-converting enzyme (ACE) inhibitors enalaprilat and ramiprilat. Nitrite, a metabolite of NO, was measured. Under baseline conditions, nitrite production in microvessels from SWOP was 30% higher than that from normal (96 ± 4 vs. 74 ± 3 pmol/mg, P < 0.01, respectively). Nitrite production in response to carbachol, bradykinin, and A23187 was also enhanced in microvessels from SWOP (P < 0.05). These enhanced responses were abolished by NG-nitro-L- arginine methyl ester (L-NAME) or the endothelial receptor-specific antagonists atropine and HOE-140. The level of eNOS protein in the SWOP myocardium was twofold higher than that in the non-SWOP myocardium. Nitrite production in response to the ACE inhibitors was greater in microvessels from SWOP. These effects were blocked by L-NAME, HOE-140, or dichloroisocoumarin (which inhibits kinin formation). We found that a brief ischemic episode induced delayed, enhanced NO production in coronary microvessels and an upregulation of eNOS protein. These findings suggest that eNOS is a mediator during the SWOP. The ability of ACE inhibitors to enhance NO release during the SWOP points to an additional clinical application for these drugs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number5
DOIs
StatePublished - May 1 2007

Fingerprint

Microvessels
Nitric Oxide Synthase
Nitrites
NG-Nitroarginine Methyl Ester
Nitric Oxide
Angiotensin-Converting Enzyme Inhibitors
Calcimycin
Carbachol
Bradykinin
Myocardium
Myocardial Ischemic Preconditioning
Enalaprilat
Kinins
Calcium Ionophores
Nitric Oxide Synthase Type III
Coronary Occlusion
Atropine
Left Ventricular Function
Reperfusion
Endothelium

All Science Journal Classification (ASJC) codes

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

Keywords

  • Angiotensin-converting enzyme inhibitors
  • Coronary circulation
  • Endothelium
  • Ischemic preconditioning
  • Nitric oxide

Cite this

Kim, Song Jung ; Zhang, Xiaoping ; Xu, Xiaobin ; Chen, Alice ; Gonzalez, Joaquin B. ; Koul, Sharat ; Vijayan, Kalpana ; Crystal, George J. ; Vatner, Stephen ; Hintze, Thomas H. / Evidence for enhanced eNOS function in coronary microvessels during the second window of protection. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 292, No. 5.
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abstract = "Nitric oxide (NO) derived from endothelial NO synthase (NOS) (eNOS) has been identified as a trigger for the second window of protection (SWOP), but its role as a mediator during the SWOP is a matter of debate. Eighteen mongrel dogs were chronically instrumented to measure left ventricular function, coronary blood flow, and wall thickening. Myocardial preconditioning was induced by 10 min coronary artery occlusion. After 24 h of reperfusion (during the SWOP), the hearts were excised. Coronary microvessels were isolated and incubated in presence of 1) the endothelium-dependent agonists carbachol and bradykinin, 2) the calcium ionophore A23187, and 3) the angiotensin-converting enzyme (ACE) inhibitors enalaprilat and ramiprilat. Nitrite, a metabolite of NO, was measured. Under baseline conditions, nitrite production in microvessels from SWOP was 30{\%} higher than that from normal (96 ± 4 vs. 74 ± 3 pmol/mg, P < 0.01, respectively). Nitrite production in response to carbachol, bradykinin, and A23187 was also enhanced in microvessels from SWOP (P < 0.05). These enhanced responses were abolished by NG-nitro-L- arginine methyl ester (L-NAME) or the endothelial receptor-specific antagonists atropine and HOE-140. The level of eNOS protein in the SWOP myocardium was twofold higher than that in the non-SWOP myocardium. Nitrite production in response to the ACE inhibitors was greater in microvessels from SWOP. These effects were blocked by L-NAME, HOE-140, or dichloroisocoumarin (which inhibits kinin formation). We found that a brief ischemic episode induced delayed, enhanced NO production in coronary microvessels and an upregulation of eNOS protein. These findings suggest that eNOS is a mediator during the SWOP. The ability of ACE inhibitors to enhance NO release during the SWOP points to an additional clinical application for these drugs.",
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Evidence for enhanced eNOS function in coronary microvessels during the second window of protection. / Kim, Song Jung; Zhang, Xiaoping; Xu, Xiaobin; Chen, Alice; Gonzalez, Joaquin B.; Koul, Sharat; Vijayan, Kalpana; Crystal, George J.; Vatner, Stephen; Hintze, Thomas H.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 5, 01.05.2007.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for enhanced eNOS function in coronary microvessels during the second window of protection

AU - Kim, Song Jung

AU - Zhang, Xiaoping

AU - Xu, Xiaobin

AU - Chen, Alice

AU - Gonzalez, Joaquin B.

AU - Koul, Sharat

AU - Vijayan, Kalpana

AU - Crystal, George J.

AU - Vatner, Stephen

AU - Hintze, Thomas H.

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N2 - Nitric oxide (NO) derived from endothelial NO synthase (NOS) (eNOS) has been identified as a trigger for the second window of protection (SWOP), but its role as a mediator during the SWOP is a matter of debate. Eighteen mongrel dogs were chronically instrumented to measure left ventricular function, coronary blood flow, and wall thickening. Myocardial preconditioning was induced by 10 min coronary artery occlusion. After 24 h of reperfusion (during the SWOP), the hearts were excised. Coronary microvessels were isolated and incubated in presence of 1) the endothelium-dependent agonists carbachol and bradykinin, 2) the calcium ionophore A23187, and 3) the angiotensin-converting enzyme (ACE) inhibitors enalaprilat and ramiprilat. Nitrite, a metabolite of NO, was measured. Under baseline conditions, nitrite production in microvessels from SWOP was 30% higher than that from normal (96 ± 4 vs. 74 ± 3 pmol/mg, P < 0.01, respectively). Nitrite production in response to carbachol, bradykinin, and A23187 was also enhanced in microvessels from SWOP (P < 0.05). These enhanced responses were abolished by NG-nitro-L- arginine methyl ester (L-NAME) or the endothelial receptor-specific antagonists atropine and HOE-140. The level of eNOS protein in the SWOP myocardium was twofold higher than that in the non-SWOP myocardium. Nitrite production in response to the ACE inhibitors was greater in microvessels from SWOP. These effects were blocked by L-NAME, HOE-140, or dichloroisocoumarin (which inhibits kinin formation). We found that a brief ischemic episode induced delayed, enhanced NO production in coronary microvessels and an upregulation of eNOS protein. These findings suggest that eNOS is a mediator during the SWOP. The ability of ACE inhibitors to enhance NO release during the SWOP points to an additional clinical application for these drugs.

AB - Nitric oxide (NO) derived from endothelial NO synthase (NOS) (eNOS) has been identified as a trigger for the second window of protection (SWOP), but its role as a mediator during the SWOP is a matter of debate. Eighteen mongrel dogs were chronically instrumented to measure left ventricular function, coronary blood flow, and wall thickening. Myocardial preconditioning was induced by 10 min coronary artery occlusion. After 24 h of reperfusion (during the SWOP), the hearts were excised. Coronary microvessels were isolated and incubated in presence of 1) the endothelium-dependent agonists carbachol and bradykinin, 2) the calcium ionophore A23187, and 3) the angiotensin-converting enzyme (ACE) inhibitors enalaprilat and ramiprilat. Nitrite, a metabolite of NO, was measured. Under baseline conditions, nitrite production in microvessels from SWOP was 30% higher than that from normal (96 ± 4 vs. 74 ± 3 pmol/mg, P < 0.01, respectively). Nitrite production in response to carbachol, bradykinin, and A23187 was also enhanced in microvessels from SWOP (P < 0.05). These enhanced responses were abolished by NG-nitro-L- arginine methyl ester (L-NAME) or the endothelial receptor-specific antagonists atropine and HOE-140. The level of eNOS protein in the SWOP myocardium was twofold higher than that in the non-SWOP myocardium. Nitrite production in response to the ACE inhibitors was greater in microvessels from SWOP. These effects were blocked by L-NAME, HOE-140, or dichloroisocoumarin (which inhibits kinin formation). We found that a brief ischemic episode induced delayed, enhanced NO production in coronary microvessels and an upregulation of eNOS protein. These findings suggest that eNOS is a mediator during the SWOP. The ability of ACE inhibitors to enhance NO release during the SWOP points to an additional clinical application for these drugs.

KW - Angiotensin-converting enzyme inhibitors

KW - Coronary circulation

KW - Endothelium

KW - Ischemic preconditioning

KW - Nitric oxide

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