Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression
J. Clin. Invest. Masaki Ieda, et al. 113:876 doi:10.1172/JCI19480 [
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Figure 4Disruption of ET-1, but not of angiotensinogen, reduces NGF expression, sympathetic nerve density, and norepinephrine concentration in murine hearts. (A) NGF expression in
Edn1+/+,
Edn1–/–,
Atg+/+, and
Atg–/– hearts at E18.5 was determined by quantitative RT-PCR (
n = 10). (B) Neurotrophin-3 (NT-3) expression in the heart was measured by quantitative RT-PCR. The same reverse transcription products used in A were analyzed. (
n = 10.) (C) Immunostaining for GAP43, PGP9.5, and TH in the heart. Nerves were restricted to the epicardium in both genotypes, and levels of GAP43, PGP9.5, and TH were lower in
Edn1–/– mice, but not in
Atg–/– mice, compared with WT littermates. (D–F) The immunopositive nerve areas for GAP43, PGP9.5, and TH were determined using NIH Image (
n = 8). (G) Cardiac norepinephrine (NE) concentrations were measured by HPLC (
n = 10). *
P < 0.0001; **
P < 0.005;
#P < 0.01. NS, not significant. Scale bar: 100 μm.
