Epinephrine is required for normal cardiovascular responses to stress in the phenylethanolamine N-methyltransferase knockout mouse.
BACKGROUND
Epinephrine (EPI) is an important neurotransmitter and hormone. Its role in regulating cardiovascular function at rest and with stress is unclear, however.


RESULTS
An epinephrine-deficient mouse model was generated in which the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase was knocked out (KO). Blood pressure and heart rate were monitored by telemetry at rest and during graded treadmill exercise. Cardiac structure and function were evaluated by echocardiography in mice under 1 of 2 conditions: unstressed and lightly anesthetized or restrained and awake. In KO mice, resting cardiovascular function, including blood pressure, heart rate, and cardiac output, was the same as that in wild-type mice, and the basal norepinephrine plasma level was normal. However, inhibition of sympathetic innervation with the ganglion blocker hexamethonium caused a 54% smaller decrease in blood pressure in KO mice, and treadmill exercise caused an 11% higher increase in blood pressure, both suggesting impaired vasodilation in KO mice. Interestingly, phenylethanolamine N-methyltransferase KO did not change the heart rate response to ganglionic blockade and exercise. By echocardiography, KO mice had an increased ratio of left ventricular posterior wall thickness to internal dimensions but did not have cardiac hypertrophy, suggesting concentric remodeling in the KO heart. Finally, in restrained, awake KO mice, heart rate and ejection fraction remained normal, but cardiac output was significantly reduced because of diminished end-diastolic volume.


CONCLUSIONS
Our data suggest that epinephrine is required for normal blood pressure and cardiac filling responses to stress but is not required for tachycardia during stress or normal cardiovascular function at rest.
Bao
Xuping
X
Department of Medicine, University of California San Diego, USA. xbao@ucsd.edu
Lu
Chuanyi M
CM
Liu
Fujun
F
Gu
Yusu
Y
Dalton
Nancy D
ND
Zhu
Bo-Qing
BQ
Foster
Elyse
E
Chen
Ju
J
Karliner
Joel S
JS
Ross
John
J
Simpson
Paul C
PC
Ziegler
Michael G
MG
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004837:Epinephrine / Q000627:therapeutic use*; D005080:Exercise Test; D015698:Genomic Library; D005838:Genotype; D006334:Heart Function Tests; D006339:Heart Rate / Q000502:physiology*; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010625:Phenylethanolamine N-Methyltransferase / Q000172:deficiency*; D016133:Polymerase Chain Reaction; D013312:Stress, Physiological; D013610:Tachycardia
D010625:Phenylethanolamine N-Methyltransferase; D004837:Epinephrine