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

• Published in: Cardiovascular research 1999-06, Vol.42 (3), p.627-635
• Main Authors: GABALLA, M. A, RAYA, T. E, HOOVER, C. A, GOLDMAN, S
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; Analysis of Variance; Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary heart disease; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Guanidines - pharmacology; Heart; Hemodynamics - drug effects; Isoproterenol - pharmacology; Medical sciences; Myocardial Infarction - enzymology; Myocardial Infarction - physiopathology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/S0008-6363(98)00343-5

To examine the relative roles of eNOS and iNOS (endothelial and inducible nitric oxide synthases) on basal and beta-adrenergic receptor (beta-AR)-stimulated arterial hemodynamic responses after myocardial infarction (MI). 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. 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) micrograms/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. (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 beta-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 beta-AR-activation of eNOS