© 1999 by European Society of Cardiology
Copyright © 1999, European Society of Cardiology
Effects of endothelial and inducible nitric oxide synthases inhibition on circulatory function in rats after myocardial infarction
Department of Internal Medicine, Veterans Administration Medical Center, Cardiology Section, 111 C 3601 S. 6th Ave., Tucson AZ 85723, USA
* Corresponding author. Tel.: +1-520-629-4624; fax: +1-520-629-4636. E-mail address: mgaballa@u.arizona.edu (M.A. Gaballa)
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 NG-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 dose 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.
KEYWORDS Blood flow; Heart failure; β-Adrenergic receptors; Nitric oxide
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