TY - JOUR
T1 - Systemic inhibition of nitric oxide synthase unmasks neural constraint of maximal myocardial blood flow in humans
AU - Kaufmann, Philipp A.
AU - Rimoldi, Ornella
AU - Gnecchi-Ruscone, Tomaso
AU - Bonser, Robert S.
AU - Lüscher, Thomas F.
AU - Camici, Paolo G.
PY - 2004/9/14
Y1 - 2004/9/14
N2 - Background-Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. Methods and Results-MBF (mL · min-1 · g-1) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and 15O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg NG-monomethyl-L- arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n= 13), 10 mg/kg L-NMMA; group 4 (n= 8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%, P
AB - Background-Nitric oxide (NO) is an endothelial mediator that regulates vascular smooth muscle tone, but it may exert its cardiovascular action also by modulating the autonomic control of vasomotor tone. We assessed the effect of simultaneous inhibition of both endothelial (eNOS) and neuronal (nNOS) NO synthase isoforms on myocardial blood flow (MBF) and coronary flow reserve (CFR) in volunteers and in (denervated) transplant recipients. Methods and Results-MBF (mL · min-1 · g-1) was measured at rest and during adenosine-induced hyperemia with positron emission tomography and 15O-labeled water. CFR was calculated as adenosine/resting MBF. Measurements were repeated during one of the following intravenous infusions: group 1 (n=12), saline; group 2 (n=9), 3 mg/kg NG-monomethyl-L- arginine (L-NMMA), which crosses the blood-brain barrier and inhibits both eNOS and nNOS; group 3 (n= 13), 10 mg/kg L-NMMA; group 4 (n= 8), phenylephrine titrated to simulate the hemodynamic changes in group 3; and group 5 (n=6), 10 mg/kg L-NMMA infused into the heart transplant recipients. After intervention, hyperemic MBF and CFR were unchanged in groups 1, 2, and 4. By contrast, both hyperemic MBF (+53%, P
KW - Blood flow
KW - Imaging
KW - Nitric oxide
KW - Synthase
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U2 - 10.1161/01.CIR.0000141294.25130.54
DO - 10.1161/01.CIR.0000141294.25130.54
M3 - Article
C2 - 15353503
AN - SCOPUS:4544363242
VL - 110
SP - 1431
EP - 1436
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 11
ER -