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Lesions of catecholamine neurons in the NTS lead to cardiac damage and sudden death in rats
Author(s) -
Talman William T.,
Zhang Wei,
Nitschke Dragon Deidre,
Lin LiHsien
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.963.1
Subject(s) - tyrosine hydroxylase , catecholamine , saporin , catecholaminergic cell groups , endocrinology , medicine , receptor , blood pressure , baroreflex , mean arterial pressure , catecholaminergic , heart rate , dopamine , immunology , antibody , monoclonal antibody , immunotoxin
We have shown that selective lesions of nucleus tractus solitarii (NTS) neurons that express NK1 receptors lead to loss of baroreflexes, labile arterial pressure, myocardial lesions and sudden death. Because selective destruction of NTS catecholaminergic neurons expressing tyrosine hydroxylase (TH) also causes lability of arterial pressure and loss of baroreflexes, we sought to test the hypothesis that cardiac lesions and lability are not dependent on specific interruption of NK1 receptor transmission. To selectively kill TH neurons in NTS we microinjected anti‐dopamine β hydroxylase (21ng/200nl) conjugated to saporin (anti‐DBH‐SAP) into NTS. Bilateral injections in 5 rats led to lability of arterial pressure (standard deviation of mean arterial pressure of 14.6 ± 4.1 mmHg), and one rat died suddenly 9 days after injection. All treated animals demonstrated microscopic myocardial necrosis as we have reported with lesions of NTS neurons with NK1 receptors. After injection of the toxin unilaterally in NTS immunofluorescent staining confirmed that anti‐DBH‐SAP injected into the NTS decreased neurons and fibers that contain TH and DBH in the injected side of the NTS. These findings contrast to the effect of SSP‐SAP on TH in NTS and provide an excellent means to compare and contrast effects of specific cellular loss on cardiac function. This work was supported by NIH HL59593, NIH HL088090 and VA Merit Review.