Lack of correlation between Myocardial nitric oxide and cyclic guanosine monophosphate content in both nitrate-tolerant and -nontolerant rats

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Abstract

We studied the effect of nitroglycerin (NTG) on cardiac nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) content in nitrate-tolerant/nontolerant rats in vivo. The effect of the pharmacological blockade of endogenous NO synthesis and the effect of exogenous NO on cardiac cGMP were also examined. Rats were treated with 100 mg/kg of NTG and corresponding vehicle s.c. three times a day for 2.5 days to induce NTG-tolerance/nontolerance. Rats were then administered a single dose of s.c. 100 mg/kg of NTG to test the effect of NTG in tolerant/nontolerant states, respectively. Nontolerant rats treated with vehicle were controls, and nontolerant rats treated with the NO synthesis inhibitor NG-nitro-L-arginine (LNNA, 20 mg/kg) were negative controls. Another group of nontolerant rats treated i.v. with the direct NO donor sodium nitroprusside (SNP, 3 mg/kg) were positive controls. Cardiac NO assessed by electron spin resonance after in vivo spin-trapping increased 100-fold (P <0.05) in the positive control, 10-fold (P <0.05) in the NTG-tolerant group, and 4-fold (P <0.05) in the single NTG group, when compared to controls. In the negative control group, NO was reduced to near the detection limit (four-fold reduction, P <0.05). Cardiac cGMP measured by radioimmunoassay was increased significantly (two-fold, P <0.05) only in the positive control group, and there were no differences among the other groups. This shows that: 1) in vivo cardiac bioconversion of NTG to NO is not impaired in nitrate tolerance; and 2) changes in cardiac NO content are not reflected by changes in cGMP content in nitrate-tolerant and -nontolerant rats. BIOCHEM PHARMACOL 56;9:1139-1144, 1998. (C) 1998 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1139-1144
Number of pages6
JournalBiochemical Pharmacology
Volume56
Issue number9
DOIs
Publication statusPublished - Nov 1 1998

Fingerprint

Cyclic GMP
Nitroglycerin
Nitrates
Rats
Nitric Oxide
Spin Trapping
Bioconversion
Control Groups
Nitric Oxide Donors
Nitroarginine
Electron Spin Resonance Spectroscopy
Nitroprusside
Radioimmunoassay
Single Nucleotide Polymorphism
Paramagnetic resonance
Limit of Detection
Pharmacology

Keywords

  • cGMP
  • Electron spin resonance
  • NG-nitro-L-arginine
  • Nitric oxide
  • Nitroglycerin
  • Tolerance

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Lack of correlation between Myocardial nitric oxide and cyclic guanosine monophosphate content in both nitrate-tolerant and -nontolerant rats",
abstract = "We studied the effect of nitroglycerin (NTG) on cardiac nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) content in nitrate-tolerant/nontolerant rats in vivo. The effect of the pharmacological blockade of endogenous NO synthesis and the effect of exogenous NO on cardiac cGMP were also examined. Rats were treated with 100 mg/kg of NTG and corresponding vehicle s.c. three times a day for 2.5 days to induce NTG-tolerance/nontolerance. Rats were then administered a single dose of s.c. 100 mg/kg of NTG to test the effect of NTG in tolerant/nontolerant states, respectively. Nontolerant rats treated with vehicle were controls, and nontolerant rats treated with the NO synthesis inhibitor NG-nitro-L-arginine (LNNA, 20 mg/kg) were negative controls. Another group of nontolerant rats treated i.v. with the direct NO donor sodium nitroprusside (SNP, 3 mg/kg) were positive controls. Cardiac NO assessed by electron spin resonance after in vivo spin-trapping increased 100-fold (P <0.05) in the positive control, 10-fold (P <0.05) in the NTG-tolerant group, and 4-fold (P <0.05) in the single NTG group, when compared to controls. In the negative control group, NO was reduced to near the detection limit (four-fold reduction, P <0.05). Cardiac cGMP measured by radioimmunoassay was increased significantly (two-fold, P <0.05) only in the positive control group, and there were no differences among the other groups. This shows that: 1) in vivo cardiac bioconversion of NTG to NO is not impaired in nitrate tolerance; and 2) changes in cardiac NO content are not reflected by changes in cGMP content in nitrate-tolerant and -nontolerant rats. BIOCHEM PHARMACOL 56;9:1139-1144, 1998. (C) 1998 Elsevier Science Inc.",
keywords = "cGMP, Electron spin resonance, NG-nitro-L-arginine, Nitric oxide, Nitroglycerin, Tolerance",
author = "T. Csont and T. P{\'a}li and Z. Szilv{\'a}ssy and P. Ferdin{\'a}ndy",
year = "1998",
month = "11",
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doi = "10.1016/S0006-2952(98)00167-1",
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T1 - Lack of correlation between Myocardial nitric oxide and cyclic guanosine monophosphate content in both nitrate-tolerant and -nontolerant rats

AU - Csont, T.

AU - Páli, T.

AU - Szilvássy, Z.

AU - Ferdinándy, P.

PY - 1998/11/1

Y1 - 1998/11/1

N2 - We studied the effect of nitroglycerin (NTG) on cardiac nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) content in nitrate-tolerant/nontolerant rats in vivo. The effect of the pharmacological blockade of endogenous NO synthesis and the effect of exogenous NO on cardiac cGMP were also examined. Rats were treated with 100 mg/kg of NTG and corresponding vehicle s.c. three times a day for 2.5 days to induce NTG-tolerance/nontolerance. Rats were then administered a single dose of s.c. 100 mg/kg of NTG to test the effect of NTG in tolerant/nontolerant states, respectively. Nontolerant rats treated with vehicle were controls, and nontolerant rats treated with the NO synthesis inhibitor NG-nitro-L-arginine (LNNA, 20 mg/kg) were negative controls. Another group of nontolerant rats treated i.v. with the direct NO donor sodium nitroprusside (SNP, 3 mg/kg) were positive controls. Cardiac NO assessed by electron spin resonance after in vivo spin-trapping increased 100-fold (P <0.05) in the positive control, 10-fold (P <0.05) in the NTG-tolerant group, and 4-fold (P <0.05) in the single NTG group, when compared to controls. In the negative control group, NO was reduced to near the detection limit (four-fold reduction, P <0.05). Cardiac cGMP measured by radioimmunoassay was increased significantly (two-fold, P <0.05) only in the positive control group, and there were no differences among the other groups. This shows that: 1) in vivo cardiac bioconversion of NTG to NO is not impaired in nitrate tolerance; and 2) changes in cardiac NO content are not reflected by changes in cGMP content in nitrate-tolerant and -nontolerant rats. BIOCHEM PHARMACOL 56;9:1139-1144, 1998. (C) 1998 Elsevier Science Inc.

AB - We studied the effect of nitroglycerin (NTG) on cardiac nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) content in nitrate-tolerant/nontolerant rats in vivo. The effect of the pharmacological blockade of endogenous NO synthesis and the effect of exogenous NO on cardiac cGMP were also examined. Rats were treated with 100 mg/kg of NTG and corresponding vehicle s.c. three times a day for 2.5 days to induce NTG-tolerance/nontolerance. Rats were then administered a single dose of s.c. 100 mg/kg of NTG to test the effect of NTG in tolerant/nontolerant states, respectively. Nontolerant rats treated with vehicle were controls, and nontolerant rats treated with the NO synthesis inhibitor NG-nitro-L-arginine (LNNA, 20 mg/kg) were negative controls. Another group of nontolerant rats treated i.v. with the direct NO donor sodium nitroprusside (SNP, 3 mg/kg) were positive controls. Cardiac NO assessed by electron spin resonance after in vivo spin-trapping increased 100-fold (P <0.05) in the positive control, 10-fold (P <0.05) in the NTG-tolerant group, and 4-fold (P <0.05) in the single NTG group, when compared to controls. In the negative control group, NO was reduced to near the detection limit (four-fold reduction, P <0.05). Cardiac cGMP measured by radioimmunoassay was increased significantly (two-fold, P <0.05) only in the positive control group, and there were no differences among the other groups. This shows that: 1) in vivo cardiac bioconversion of NTG to NO is not impaired in nitrate tolerance; and 2) changes in cardiac NO content are not reflected by changes in cGMP content in nitrate-tolerant and -nontolerant rats. BIOCHEM PHARMACOL 56;9:1139-1144, 1998. (C) 1998 Elsevier Science Inc.

KW - cGMP

KW - Electron spin resonance

KW - NG-nitro-L-arginine

KW - Nitric oxide

KW - Nitroglycerin

KW - Tolerance

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