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Impaired cardiac norepinephrine transport in the hypertensive rat
Author(s) -
Shanks Julia,
Mane Saras,
Ryan Rebecca,
Paterson David
Publication year - 2012
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.26.1_supplement.1092.5
Subject(s) - medicine , norepinephrine transporter , reuptake , endocrinology , norepinephrine , sympathetic nervous system , heart rate , stellate ganglion , dopamine , blood pressure , serotonin , receptor , alternative medicine , pathology
Hypertension is associated with upregulation of sympathetic cardiac responsiveness both pre and post‐synaptically. Enhanced cardiac norepinephrine (NE) release has been reported in prehypertensive and hypertensive spontaneously hypertensive rats (SHR) compared to normotensive controls (WKY). This phenotype might result from defective NET‐1 transport (uptake‐1). A novel fluorescent substrate of the NE reuptake transporter (NET) was used to investigate NE reuptake kinetics in isolated sympathetic stellate and superior cervical ganglia (SCG) neural cells from SHRs and age‐matched WKY rats. Pre‐hypertensive SHR, and those with established hypertension were studied. Decreased rate of NET (~24%) in stellate ganglion neurons from the SHR at both developmental ages (4 week SHR, n=24, WKY, n=21, P <0.05, unpaired t test, 16 week SHR, n=20, WKY, n=19, P <0.05, unpaired t test) was observed when compared to the WKY response. No difference in re‐uptake rate was seen in cells from the SCG, a major sympathetic ganglia whose innervations predominantly supplies the face. Electrical stimulation of stellate neurons exacerbated the re‐uptake difference of NE between SHR and WKY cells. These results suggest that cardiac sympathetic hyper‐responsiveness is in part due to slowed NE reuptake in the SHR, and this defect occurs before the actual onset of hypertension. Furthermore the NET impairment was not observed in another (non‐cardiac) sympathetic ganglia.