Multi-parameter in vivo cardiac magnetic resonance imaging demonstrates normal perfusion reserve despite severely attenuated beta-adrenergic functional response in neuronal nitric oxide synthase knockout mice.
OBJECTIVE
The role of neuronal nitric oxide synthase (nNOS) in regulating contractile function remains controversial, and in regulating myocardial perfusion is uninvestigated. We used magnetic resonance imaging (MRI) to phenotype nNOS(-/-) and wild-type (WT) mice regarding left ventricular (LV) structure, baseline function, beta-adrenergic responsiveness, and perfusion reserve.


RESULTS
Cine MRI showed higher LV mass to end-diastolic volume ratio (2.3 +/- 0.2 mg/microL nNOS(-/-) vs. 1.7 +/- 0.1 mg/microL WT; P=0.032) and LV ejection fraction (64.9 +/- 2.1% nNOS(-/-) vs. 55.8 +/- 1.1% WT; P = 0.003) in nNOS(-/-). Myocardial tagging demonstrated similar baseline systolic circumferential strain (Ecc) in nNOS(-/-) and WT. With dobutamine, the normal change in Ecc was nearly absent in nNOS(-/-) (-0.5 +/- 0.3% nNOS(-/-) vs. -2.2 +/- 0.3% WT; P = 0.001), and the systolic strain rate (dEcc/dt) response to dobutamine seen in WT was reduced in nNOS(-/-) (-29 +/- 13%/s nNOS(-/-) vs. -106+/-16%/s WT; P = 0.001). Diastolic strain rate increased significantly with dobutamine only in WT. Arterial spin labelling showed that baseline perfusion and perfusion reserve with either dobutamine or an adenosine receptor agonist are normal in nNOS(-/-).


CONCLUSIONS
MRI provides non-invasive in vivo evidence that nNOS does not play a role in basal contractile function or myocardial perfusion, but is required for increasing cardiac inotropy and lusitropy upon beta-adrenergic stimulation.
Vandsburger
Moriel H
MH
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
French
Brent A
BA
Helm
Patrick A
PA
Roy
Rene Jack
RJ
Kramer
Christopher M
CM
Young
Alistair A
AA
Epstein
Frederick H
FH
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002306:Cardiac Volume / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004280:Dobutamine / Q000494:pharmacology; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology; D018810:Magnetic Resonance Angiography; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052248:Nitric Oxide Synthase Type I / Q000502:physiology*; D010641:Phenotype; D010880:Piperidines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D013599:Systole; D014664:Vasodilation / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000201:enzymology* / Q000473:pathology
C510376:ATL 313; D000318:Adrenergic beta-Agonists; D010880:Piperidines; D058906:Purinergic P1 Receptor Agonists; D004280:Dobutamine; D052248:Nitric Oxide Synthase Type I