Inhibition of Nitric Oxide Synthesis Reduces Coronary Blood Flow Response But Does Not Increase Cardiac Contractile Response to β-Adrenergic Stimulation in Normal Dogs

• Published in: Journal of cardiovascular pharmacology Vol. 27; no. 2; pp. 247 - 254
• Main Authors: Kaneko, Haruo, Endo, Takao, Kiuchi, Kaname, Hayakawa, Hirokazu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Lippincott-Raven Publishers 01-02-1996; Hagerstown, MD Lippincott
• Subjects: Acetylcholine - pharmacology; Adrenergic beta-Agonists - pharmacology; Animals; Biological and medical sciences; Coronary Circulation - drug effects; Dogs; Female; Fundamental and applied biological sciences. Psychology; Heart; Heart Rate - drug effects; Hemodynamics - drug effects; Hypertrophy, Left Ventricular - physiopathology; Hypertrophy, Left Ventricular - prevention & control; Isoproterenol - pharmacology; Male; Myocardial Contraction - drug effects; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Vertebrates: cardiovascular system; Fissipedia; Regional blood flow; Carnivora; Agonist; Coronary artery; Contractility; Biological activity; β-Adrenergic receptor; Vertebrata; Mammalia; Animal; Nitrogen monoxide; Dog
• DOI: 10.1097/00005344-199602000-00011
• EISSN: 1533-4023
• ISSN: 0160-2446

Whether the nitric oxide (NO) system constitutively present in the normal myocardium and resistance coronary vessels regulates basal cardiac contractility and coronary blood flow (CBF), as well as their responses to β-adrenergic stimulation in intact heart, remains controversial. We examined the effects of low and high doses of N-nitro-L-arginine methyl ester (L-NAME) (10 and 100 μg/kg/min for 10 min), an NO synthase inhibitor, as well as D-enantiomer administered into left circumflex (LCX) artery on responses of left ventricular (LV) dP/dt, regional wall thickening in LCX region and LCX blood flow to graded intracoronary doses of isoproterenol (ISO 0.002-0.016 μg/kg/min) in normal dogs. Intracoronary L-NAME, which was associated with dose-related reductions in acetylcholine (ACh)-induced coronary vasodilation, significantly reduced baseline LCX blood flow and its response to ISO. However, L-NAME did not change baseline LV contractility as assessed by LV dP/dt and regional wall thickening, nor did it increase its response to ISO. D-Enantiomer was ineffective in reducing baseline LCX blood flow as well as its response to ISO. These results indicate that constitutive NO formation in the vasculature contributes to basal coronary vascular tone as well as resistance adjustments during β-adrenergic stimulation. However, NO formation in the normal myocardium did not influence basal cardiac contractility; nor did it increase cardiac response to β-adrenergic stimulation.