(Circulation. 1995;92:2198-2203.)
© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide Inhibits the Positive Inotropic Response to ß-Adrenergic Stimulation in Humans With Left Ventricular Dysfunction
Presented in part at the 67th Scientific Sessions of the American Heart Association, Dallas, Tex, November 14-17, 1994, and published in abstract form (Circulation. 1994;90[pt 2]:I-193).
From the Cardiomyopathy Center, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Dr Wilson S. Colucci, Cardiomyopathy Center, Boston University School of Medicine, 80 E Concord St, Boston, MA 02118.
Background Nitric oxide (NO) attenuates the contractile response to ß-adrenergic stimulation in cultured cardiac myocytes in vitro and in myocardium in vivo. We tested the hypothesis that NO synthesized in the heart inhibits the positive inotropic response to ß-adrenergic stimulation in humans with left ventricular (LV) dysfunction.
Methods and Results Patients with various degrees of LV dysfunction and free from epicardial coronary artery disease were instrumented with an infusion catheter in the left main coronary artery and a high-fidelity micromanometer-tipped catheter in the LV. Measurements included LV pressure, aortic pressure, heart rate, and LV peak +dP/dt. In eight subjects, dobutamine was infused via the left main coronary artery (25 or 50 µg/min) before and concurrent with intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 20 µmol/min for 10 minutes). In six other subjects, dobutamine was infused (6, 10, or 15 µg · kg-1 · min-1) via a peripheral vein. Intracoronary (n=8) dobutamine infusions increased LV peak +dP/dt by an average of 33±3%. The intracoronary infusion of L-NMMA had no effect on baseline LV peak +dP/dt, LV systolic or end-diastolic pressures, aortic pressure, or heart rate. The intracoronary infusion of L-NMMA, concurrent with a second infusion of dobutamine, potentiated the +dP/dt response to dobutamine by 30±10% (P<.04 versus dobutamine alone). The intracoronary infusion of L-NMMA likewise potentiated the +dP/dt response to the peripheral infusion of dobutamine by 37±18%.
Conclusions Nitric oxide produced in the heart attenuates the positive inotropic response to ß-adrenergic stimulation in humans with LV dysfunction. NO may contribute to ß-adrenergic hyporesponsiveness in patients with LV dysfunction.
Key Words: nervous system • nitric oxide • L-NMMA • receptors • adrenergic • beta • contractility • heart failure
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