Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction

Mohamed A. Gaballa, Thomas E. Raya, Craig A. Hoover, Steven Goldman

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Objectives: To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and β-adrenergic receptor (β-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). Methods: Left ventricular (LV) pressures and steady-state and pulsatile arterial hemodynamics were measured at baseline, and after acute NOS inhibition with either N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) or iNOS inhibition with aminoguanidine (AG, 75 mg/kg) in sham-operated and MI Sprague-Dawley rats. Results: In sham rats, L-NAME decreased (P<0.05) peak positive LV dP/dt and aortic blood velocity by 19% and 53%, respectively, and increased (P<0.05) mean arterial pressure (MAP), systemic vascular resistance, and LV end-diastolic pressure (EDP) by 20, 189 and 89%, respectively. The frequency-dependent components of hemodynamics including aortic input impedance modulus, characteristic impedance, and phase shift were increased (P<0.05) with L-NAME, while pulsatile power was decreased (P<0.05). AG increased (P<0.05) aortic input impedance modulus and characteristic impedance but had no effect on any other hemodynamic variable. In MI rats, L-NAME decreased (P<0.05) LV dP/dt and aortic blood velocity by 22 and 55%; respectively, and increased (P<0.05) SVR by 108%. There was no effect of L-NAME on MAP or LV EDP in MI rats. After MI, AG increased (P<0.05) heart rate and LV dP/dt but had no effect on other LV or pulsatile hemodynamic variables. Compared to Sham rats, heart rate, LV dP/dt, and blood velocity-isoproterenol close responses were shifted downward (P<0.05), while SVR-isoproterenol dose response was shifted upward (P<0.05) in MI rats. In sham rats, L-NAME potentiated (P<0.05, at >10-2 μg/kg) the isoproterenol- induced increase in LV dP/dt and aortic blood velocity, and potentiated (P<0.05) the isoproterenol-induced decline in SVR. AS expected, AG had no effects on isoproterenol-stimulated hemodynamics in sham rats. After MI, there was no effect of L-NAME or AG on isoproterenol-stimulated hemodynamics. Conclusions: (1) Circulatory and cardiac responses to inhibition of NO by L- NAME suggest that eNOS, but not iNOS, is the principal regulator of integrated arterial hemodynamic function in rats. (2) Both basal and β-AR- stimulated NO regulation of hemodynamic are attenuated after MI. (3) The attenuation of arterial hemodynamic effects after isoproterenol is mediated, in part, by alterations in the β-AR-activation of eNOS system after MI.

Original languageEnglish (US)
Pages (from-to)627-635
Number of pages9
JournalCardiovascular Research
Volume42
Issue number3
DOIs
StatePublished - Jun 1999
Externally publishedYes

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Nitric Oxide Synthase Type III
Nitric Oxide Synthase Type II
NG-Nitroarginine Methyl Ester
Hemodynamics
Myocardial Infarction
Isoproterenol
Ventricular Pressure
Adrenergic Receptors
Sprague Dawley Rats

Keywords

  • β-Adrenergic receptors
  • Blood flow
  • Heart failure
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction. / Gaballa, Mohamed A.; Raya, Thomas E.; Hoover, Craig A.; Goldman, Steven.

In: Cardiovascular Research, Vol. 42, No. 3, 06.1999, p. 627-635.

Research output: Contribution to journalArticle

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abstract = "Objectives: To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and β-adrenergic receptor (β-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). Methods: Left ventricular (LV) pressures and steady-state and pulsatile arterial hemodynamics were measured at baseline, and after acute NOS inhibition with either N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) or iNOS inhibition with aminoguanidine (AG, 75 mg/kg) in sham-operated and MI Sprague-Dawley rats. Results: In sham rats, L-NAME decreased (P<0.05) peak positive LV dP/dt and aortic blood velocity by 19{\%} and 53{\%}, respectively, and increased (P<0.05) mean arterial pressure (MAP), systemic vascular resistance, and LV end-diastolic pressure (EDP) by 20, 189 and 89{\%}, respectively. The frequency-dependent components of hemodynamics including aortic input impedance modulus, characteristic impedance, and phase shift were increased (P<0.05) with L-NAME, while pulsatile power was decreased (P<0.05). AG increased (P<0.05) aortic input impedance modulus and characteristic impedance but had no effect on any other hemodynamic variable. In MI rats, L-NAME decreased (P<0.05) LV dP/dt and aortic blood velocity by 22 and 55{\%}; respectively, and increased (P<0.05) SVR by 108{\%}. There was no effect of L-NAME on MAP or LV EDP in MI rats. After MI, AG increased (P<0.05) heart rate and LV dP/dt but had no effect on other LV or pulsatile hemodynamic variables. Compared to Sham rats, heart rate, LV dP/dt, and blood velocity-isoproterenol close responses were shifted downward (P<0.05), while SVR-isoproterenol dose response was shifted upward (P<0.05) in MI rats. In sham rats, L-NAME potentiated (P<0.05, at >10-2 μg/kg) the isoproterenol- induced increase in LV dP/dt and aortic blood velocity, and potentiated (P<0.05) the isoproterenol-induced decline in SVR. AS expected, AG had no effects on isoproterenol-stimulated hemodynamics in sham rats. After MI, there was no effect of L-NAME or AG on isoproterenol-stimulated hemodynamics. Conclusions: (1) Circulatory and cardiac responses to inhibition of NO by L- NAME suggest that eNOS, but not iNOS, is the principal regulator of integrated arterial hemodynamic function in rats. (2) Both basal and β-AR- stimulated NO regulation of hemodynamic are attenuated after MI. (3) The attenuation of arterial hemodynamic effects after isoproterenol is mediated, in part, by alterations in the β-AR-activation of eNOS system after MI.",
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author = "Gaballa, {Mohamed A.} and Raya, {Thomas E.} and Hoover, {Craig A.} and Steven Goldman",
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pages = "627--635",
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T1 - Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction

AU - Gaballa, Mohamed A.

AU - Raya, Thomas E.

AU - Hoover, Craig A.

AU - Goldman, Steven

PY - 1999/6

Y1 - 1999/6

N2 - Objectives: To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and β-adrenergic receptor (β-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). Methods: Left ventricular (LV) pressures and steady-state and pulsatile arterial hemodynamics were measured at baseline, and after acute NOS inhibition with either N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) or iNOS inhibition with aminoguanidine (AG, 75 mg/kg) in sham-operated and MI Sprague-Dawley rats. Results: In sham rats, L-NAME decreased (P<0.05) peak positive LV dP/dt and aortic blood velocity by 19% and 53%, respectively, and increased (P<0.05) mean arterial pressure (MAP), systemic vascular resistance, and LV end-diastolic pressure (EDP) by 20, 189 and 89%, respectively. The frequency-dependent components of hemodynamics including aortic input impedance modulus, characteristic impedance, and phase shift were increased (P<0.05) with L-NAME, while pulsatile power was decreased (P<0.05). AG increased (P<0.05) aortic input impedance modulus and characteristic impedance but had no effect on any other hemodynamic variable. In MI rats, L-NAME decreased (P<0.05) LV dP/dt and aortic blood velocity by 22 and 55%; respectively, and increased (P<0.05) SVR by 108%. There was no effect of L-NAME on MAP or LV EDP in MI rats. After MI, AG increased (P<0.05) heart rate and LV dP/dt but had no effect on other LV or pulsatile hemodynamic variables. Compared to Sham rats, heart rate, LV dP/dt, and blood velocity-isoproterenol close responses were shifted downward (P<0.05), while SVR-isoproterenol dose response was shifted upward (P<0.05) in MI rats. In sham rats, L-NAME potentiated (P<0.05, at >10-2 μg/kg) the isoproterenol- induced increase in LV dP/dt and aortic blood velocity, and potentiated (P<0.05) the isoproterenol-induced decline in SVR. AS expected, AG had no effects on isoproterenol-stimulated hemodynamics in sham rats. After MI, there was no effect of L-NAME or AG on isoproterenol-stimulated hemodynamics. Conclusions: (1) Circulatory and cardiac responses to inhibition of NO by L- NAME suggest that eNOS, but not iNOS, is the principal regulator of integrated arterial hemodynamic function in rats. (2) Both basal and β-AR- stimulated NO regulation of hemodynamic are attenuated after MI. (3) The attenuation of arterial hemodynamic effects after isoproterenol is mediated, in part, by alterations in the β-AR-activation of eNOS system after MI.

AB - Objectives: To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and β-adrenergic receptor (β-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). Methods: Left ventricular (LV) pressures and steady-state and pulsatile arterial hemodynamics were measured at baseline, and after acute NOS inhibition with either N(G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/kg) or iNOS inhibition with aminoguanidine (AG, 75 mg/kg) in sham-operated and MI Sprague-Dawley rats. Results: In sham rats, L-NAME decreased (P<0.05) peak positive LV dP/dt and aortic blood velocity by 19% and 53%, respectively, and increased (P<0.05) mean arterial pressure (MAP), systemic vascular resistance, and LV end-diastolic pressure (EDP) by 20, 189 and 89%, respectively. The frequency-dependent components of hemodynamics including aortic input impedance modulus, characteristic impedance, and phase shift were increased (P<0.05) with L-NAME, while pulsatile power was decreased (P<0.05). AG increased (P<0.05) aortic input impedance modulus and characteristic impedance but had no effect on any other hemodynamic variable. In MI rats, L-NAME decreased (P<0.05) LV dP/dt and aortic blood velocity by 22 and 55%; respectively, and increased (P<0.05) SVR by 108%. There was no effect of L-NAME on MAP or LV EDP in MI rats. After MI, AG increased (P<0.05) heart rate and LV dP/dt but had no effect on other LV or pulsatile hemodynamic variables. Compared to Sham rats, heart rate, LV dP/dt, and blood velocity-isoproterenol close responses were shifted downward (P<0.05), while SVR-isoproterenol dose response was shifted upward (P<0.05) in MI rats. In sham rats, L-NAME potentiated (P<0.05, at >10-2 μg/kg) the isoproterenol- induced increase in LV dP/dt and aortic blood velocity, and potentiated (P<0.05) the isoproterenol-induced decline in SVR. AS expected, AG had no effects on isoproterenol-stimulated hemodynamics in sham rats. After MI, there was no effect of L-NAME or AG on isoproterenol-stimulated hemodynamics. Conclusions: (1) Circulatory and cardiac responses to inhibition of NO by L- NAME suggest that eNOS, but not iNOS, is the principal regulator of integrated arterial hemodynamic function in rats. (2) Both basal and β-AR- stimulated NO regulation of hemodynamic are attenuated after MI. (3) The attenuation of arterial hemodynamic effects after isoproterenol is mediated, in part, by alterations in the β-AR-activation of eNOS system after MI.

KW - β-Adrenergic receptors

KW - Blood flow

KW - Heart failure

KW - Nitric oxide

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C2 - 10533602

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VL - 42

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