Is neuropeptide Y co-released with catecholamines in experimental arterial hypertension following sinoaortic denervation?
The release of catecholamines and their coneurotransmitter neuropeptide Y (NPY) was investigated in conscious dogs with neurogenic arterial hypertension elicited by sinoaortic denervation. One month after denervation, an elevation of catecholamine levels (measured by HPLC) without elevation of NPY-like immunoreactivity (NPY-LI) levels in plasma (evaluated by RIA) has been found. This dissociation could be explained by 1) a transient release of NPY during the first weeks after surgery, 2) a depletion of neuronal NPY due to the permanent sympathetic stimulation, or 3) an insufficient increase in sympathetic tone. To test these hypotheses, we investigated the time courses of catecholamine and NPY-LI levels in arterial plasma during the first five weeks after sinoaortic denervation and responses to yohimbine (an alpha 2 antagonist which enhances transmitter release). Resting NPY-LI levels in plasma remained normal during the first five weeks after sinoaortic denervation. In normal dogs, a high dose of yohimbine (0.5 mg/kg i.v.) elevated both catecholamine (6-fold) and NPY-LI levels (1.5-fold), whereas a lower dose (0.05 mg/kg i.v.) induced a two fold elevation of catecholamine levels without changing NPY-LI concentrations. In sinoaortically denervated dogs, yohimbine elicited elevation of both catecholamines and NPY-LI whatever the dose used. Thus, neurogenic arterial hypertension in dogs seems to involve catecholamines but not NPY. Moreover, the present work suggests that a high level of sympathetic stimulation is required for a co-release of catecholamines and NPY.
Tavernier
G
G
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine.
Damase-Michel
C
C
Portolan
G
G
Tran
M A
MA
Montastruc
J L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood / Q000378:metabolism*; D003714:Denervation; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism*; D011863:Radioimmunoassay; D012849:Sinoatrial Node / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology; D015016:Yohimbine / Q000494:pharmacology
D002395:Catecholamines; D009478:Neuropeptide Y; D015016:Yohimbine