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Published on: June 18, 2012
Nitric oxide inhibits the positive inotropic response to beta-adrenergic stimulation in humans with left ventricular
1Cardiomyopathy Center, Boston University School of Medicine, MA 02118, USA.
Insights
Nitric oxide (NO) in the heart reduces the response to beta-adrenergic stimulation in patients with left ventricular (LV) dysfunction. Inhibiting NO enhances this response, suggesting NO contributes to hyporesponsiveness.
Area of Science:
- Cardiology
- Physiology
- Pharmacology
Background:
- Nitric oxide (NO) is known to reduce cardiac contractility in response to beta-adrenergic stimulation.
- This effect has been observed in cell cultures and animal models.
Purpose of the Study:
- To investigate if endogenously produced nitric oxide (NO) in the human heart inhibits the positive inotropic effects of beta-adrenergic stimulation.
- To test this in patients with left ventricular (LV) dysfunction.
Main Methods:
- Patients with LV dysfunction received dobutamine infusions (intracoronary or peripheral).
- The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), was infused intracoronary.
- Left ventricular pressure and dP/dt were measured to assess contractility.
Main Results:
- Intracoronary dobutamine increased LV peak +dP/dt by 33%.
- L-NMMA alone did not affect baseline cardiac function.
- Concurrent L-NMMA infusion potentiated dobutamine's effect on +dP/dt by 30-37%.
Conclusions:
- Heart-derived nitric oxide (NO) attenuates the positive inotropic response to beta-adrenergic stimulation in humans with LV dysfunction.
- NO may play a role in the reduced responsiveness to beta-adrenergic agents seen in these patients.
Background:
Nitric oxide (NO) attenuates the contractile response to beta-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 beta-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 micrograms/min) before and concurrent with intracoronary infusion of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 20 mumol/min for 10 minutes). In six other subjects, dobutamine was infused (6, 10, or 15 micrograms.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 beta-adrenergic stimulation in humans with LV dysfunction. NO may contribute to beta-adrenergic hyporesponsiveness in patients with LV dysfunction.
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